5.3 - structural proteins

Assembly of a microtubule begins with the end-to-end association of tubulin dimers to form a short linear protofilament. Protofilaments then align side-to-side in a curved sheet, which wraps around on itself to form a hollow tube of 13 protofilaments (Fig. 5.22). The microtubule extends as tubulin dimers add to both ends. Like an actin filament, the microtubule is polar and one end grows more rapidly. The (+) end, terminating in β-tubulin, grows about twice as fast as the (−) or α-tubulin end because tubulin dimers bind preferentially to the (+) end.

protofilament One of the 13 linear polymers of tubulin subunits that forms a microtubule.

Actin filament dynamics in cell crawling

(a) Scanning electron micrograph of crawling cells. The leading edges of the cells (lower left) are ruffled where they have become detached from the surface and are in the process of extending. The trailing edges or tails of the cells, still attached to the surface (upper right), are gradually pulled toward the leading edge. The rate of actin polymerization is greatest at the leading edge.

Assembly of a microtubule

(a) αβ Dimers of tubulin initially form a linear protofilament. Protofilaments associate side by side, ultimately forming a tube. Tubulin dimers can add to either end of the microtubule, but growth is about twice as fast at the (+) end. (b) Cryoelectron microscopy view of a microtubule.

intermediate filaments

A 100-Å-diameter cytoskeletal element consisting of coiled-coil polypeptide chains.

microtubules

A 240-Å-diameter cytoskeletal element consisting of a hollow tube of polymerized tubulin subunits.

actin filaments - microfilaments (smallest)

A 70-Å-diameter cytoskeletal element composed of polymerized actin subunits. Also called a microfilament.

Actin filaments are most abundant

A major portion of the eukaryotic cytoskeleton consists of actin filaments, also known as microfilaments, which are polymers of the protein actin. ... polymers of the protein actin!!!! In many cells, a network of actin filaments supports the plasma membrane and therefore determines cell shape (see Fig. 2.7 and Fig. 5.14). Certain proteins cross-link individual actin polymers to help form bundles of filaments, thereby increasing their strength.

Calculations suggest that under cellular conditions, the equilibrium between monomeric actin and polymeric actin favors the polymer. However, the growth of actin filaments in vivo is limited by capping proteins that bind to and block further polymerization at the (+) or (−) ends. A process that removes an actin filament cap will target growth to the uncapped end. New actin filament growth can also occur as branches form along existing microfilaments.

A supply of actin monomers to support actin filament growth in one area must come at the expense of actin filament disassembly elsewhere. In a cell, certain proteins sever actin filaments by binding to a polymerized actin subunit and inducing a small structural change that weakens actin-actin interactions and thereby increases the likelihood that the filament will break at that point. Actin subunits can then dissociate from the newly exposed ends unless they are subsequently capped.

Monomeric actin is a globular protein with about 375 amino acids (Fig. 5.15). On its surface is a cleft in which adenosine triphosphate (ATP) binds. The adenosine group slips into a pocket on the protein, and the ribose hydroxyl groups and the phosphate groups form hydrogen bonds with the protein.

Actin monomerThis protein assumes a globular shape with a cleft where ATP (green) binds.

Actin filament assembly

An actin filament grows as subunits add to its ends. Subunits usually add more rapidly to the (+) end, which therefore grows faster than the (−) end. The original segment is shaded more darkly. Actual actin filaments are much longer than depicted here.

Perhaps due to their cable-like construction, intermediate filaments undergo less remodeling than cellular fibers constructed from globular subunits such as actin and tubulin. For example, nuclear lamins disassemble and reassemble only once during the cell cycle, when the cell divides. Keratins, as part of dead cells, remain intact for years. In the innermost layers of animal skin, epidermal cells synthesize large amounts of keratin. As layers of cells move outward and die, their keratin molecules are pushed together to form a strong waterproof coating.

Because keratin is so important for the integrity of the epidermis, mutations in keratin genes are linked to certain skin disorders. In diseases such as epidermolysis bullosa simplex (EBS), cells rupture when subject to normal mechanical stress. The result is separation of epidermal layers, which leads to blistering. The most severe cases of the disease arise from mutations in the most highly conserved regions of the keratin molecules, near the ends of the α-helical regions.

Some drugs affect microtubules Compounds that interfere with microtubule dynamics can have drastic physiological effects. One reason is that during mitosis, chromosomes separate along a spindle made of microtubules (Fig. 5.24). The drug colchicine, a product of the meadow saffron plant, causes microtubules to depolymerize, thereby blocking cell division.

Colchicine binds at the interface between α- and β-tubulin in a dimer, facing the inside of the microtubule cylinder. The bound drug may induce a slight conformational change that weakens the lateral contacts between protofilaments. If enough colchicine is present, microtubules shorten and eventually disappear. Colchicine was first used over 2000 years ago to treat gout (inflammation stemming from the precipitation of uric acid in the joints) because it inhibits the action of the white blood cells that mediate inflammation.

Collagen molecules are covalently cross-linked Trimeric collagen molecules assemble in the endoplasmic reticulum. After they are secreted from the cell, they are trimmed by proteases and align side-to-side and end-to-end to form the enormous fibers visible by electron microscopy (see Fig. 5.30). The fibers are strengthened by several kinds of cross-links. Because collagen polypeptides contain almost no cysteine, these links are not disulfide bonds. Instead, the cross-links are covalent bonds between side chains that have been chemically modified following polypeptide synthesis. For example, one kind of cross-link requires the enzyme-catalyzed oxidation of two lysine side chains, which then react to form a covalent bond. The number of these and other types of cross-links tends to increase with age, which explains why meat from older animals is tougher than meat from younger animals.

Collagen fibers have tremendous tensile strength. On a per-weight basis, collagen is stronger than steel. Not all types of collagen form thick linear fibers, however. Many nonfibrillar collagens form sheetlike networks of fibers that support layers of cells in tissues. Often, several types of collagen are found together. Not surprisingly, defects in collagen affect a variety of organ systems

bone and collagen defects

Connective tissue, such as cartilage and bone, consists of cells embedded in a matrix containing proteins (mainly collagen) and a space-filling "ground substance" (mostly polysaccharides; see Section 11.3). The polysaccharides, which are highly hydrated, are resilient and return to their original shape after being compressed. The collagen fibers are strong and relatively rigid, resisting tensile (stretching) forces. Together, the polysaccharides and collagen give ligaments (which attach bone to bone) and tendons (which join muscles to bones) the appropriate degree of resistance and flexibility. The connective tissues that surround muscles and organs contain collagen fibers arranged in sheetlike networks with similar physical properties.

In collagen, three polypeptides wind around each other to form a right-handed triple helix (Fig. 5.31b-d). The chains are parallel but staggered by one residue so that glycine appears at every position along the axis of the triple helix. The glycine residues are all located in the center of the helix, whereas all other residues are on the periphery. A look down the axis of the triple helix shows why glycine—but no other residue—occurs in the center of the helix (Fig. 5.32). The side chain of any other residue would be too large to fit. In fact, replacing glycine with alanine, the next-smallest amino acid, greatly perturbs the structure of the triple helix.

Cross-section of the collagen triple helix In this view, looking down the axis of the three-chain molecule, each ball represents an amino acid, and the bars represent peptide bonds. Glycine residues (which lack side chains and are marked by "G") are located in the center of the triple helix, whereas the side chains of other residues point outward from the triple helix.

Microtubules in a dividing cell

During mitosis, microtubules (green fluorescence) connect replicated chromosomes (blue fluorescence) to two organizing centers (red dots) at opposite sides of the cell. The microtubules disassemble and shorten to pull the chromosomes apart before the cell splits in half.

Mutations in collagen type II, a form found in cartilage, lead to osteoarthritis. This genetic disease, which becomes apparent in childhood, is distinct from the osteoarthritis that can develop later in life, often after years of wear and tear on the joints. Defects in the proteins that process collagen extracellularly and help assemble collagen fibers lead to disorders such as dermatosparaxis, which is characterized by extreme skin fragility.

Ehlers-Danlos syndrome results from abnormalities in collagen type III, a molecule that is abundant in most tissues but is scarce in skin and bone. Symptoms of this phenotypically variable disorder include easy bruising, thin or elastic skin, and joint hyperextensibility. In one form of the disease, which is accompanied by a high risk for arterial rupture, the molecular defect is a mutation in a collagen type III gene. In another form of the disease, in which individuals often suffer from scoliosis (curvature of the spine), the collagen genes are normal. In these cases, the disease results from a deficiency of lysyl oxidase, the enzyme that modifies lysine residues so that they can participate in collagen cross-links. Ehlers-Danlos syndrome is both rarer and less severe than osteogenesis imperfecta, with many affected individuals surviving to adulthood. Ehlers-Danlos syndrome A genetic disease characterized by elastic skin and joint hyperextensibility, caused by mutations in genes for collagen or collagen-processing proteins.

Disassembly of a microtubule also takes place at both ends but occurs more rapidly at the (+) end. Under conditions that favor depolymerization, the ends of the microtubule appear to fray (Fig. 5.23). This suggests that tubulin dimers do not simply dissociate individually from the microtubule ends but that the interactions between protofilaments weaken before the tubulin dimers come loose.

Electron micrograph of a depolymerizing microtubule The ends of protofilaments apparently curve away from the microtubule and separate before tubulin dimers dissociate. Under certain conditions, microtubule treadmilling can occur when tubulin subunits add to the (+) end as fast as they leave the (−) end. In vivo, the (−) ends are often anchored to some sort of organizing center in the cell. This means that most microtubule growth and regression occur at the (+) end. Microtubule dynamics are also regulated by proteins that cross-link microtubules and promote or prevent depolymerization.

Keratin is an intermediate filament

In addition to actin filaments and microtubules, eukaryotic cells—particularly those in multicellular organisms—contain intermediate filaments. With a diameter of about 100 Å, these fibers are intermediate in thickness to actin filaments and microtubules. Intermediate filaments are exclusively structural proteins. They play no part in cell motility, and unlike actin filaments and microtubules, they have no associated motor proteins. However, they do interact with actin filaments and microtubules via cross-linking proteins.

The shapes of eukaryotic cells, particularly those without an external cell wall, are determined by an intracellular network of proteins known as the cytoskeleton. Typically, three types of cytoskeletal proteins form fibers that extend throughout the cell (Fig. 5.14). These are actin filaments (with a diameter of about 70 Å), intermediate filaments (with a diameter of about 100 Å), and microtubules (with a diameter of about 240 Å).

In large multicellular organisms, fibers of the protein collagen provide structural support extracellularly. Bacterial cells also contain proteins that form structures similar to actin filaments and microtubules. In the following discussion, note how the structure of each protein influences the overall structure and flexibility of the fiber as well as the fiber's ability to disassemble and reassemble.

Vitamin C Deficiency Causes Scurvy

In the absence of ascorbate (vitamin C), collagen contains too few hydroxyproline residues and hydroxylated lysine residues, so the resulting collagen fibers are relatively weak. Ascorbate also participates in enzymatic reactions involved in fatty acid breakdown and production of certain hormones. The symptoms of ascorbate deficiency include poor wound healing, loss of teeth, and easy bleeding—all of which can be attributed to abnormal collagen synthesis—as well as lethargy and depression. Historically, ascorbate deficiency, known as scurvy, was common in sailors on long voyages where fresh fruit was unavailable. A remedy, in the form of a daily ration of limes, was discovered in the mid-eighteenth century. Unfortunately, citrus juice, which was also widely administered, proved much less effective in preventing scurvy because ascorbate is destroyed by heating and by prolonged exposure to air. For this reason, factors such as exercise and good hygiene were also believed to prevent scurvy. Fruit is not the only source of ascorbate. Most animals—with the exception of bats, guinea pigs, and primates—produce ascorbate, so a diet containing fresh meat can supply sufficient ascorbate, which is vital in locations, such as the far North, where fruit is not available. Given the presence of ascorbate in many foods, a true deficiency is rare in adults. Scurvy does still occur, however, as a side effect of general malnutrition or in individuals consuming odd diets. Fortunately, the symptoms of scurvy, which is otherwise fatal, can be easily reversed by administering ascorbate or consuming fresh food.

Model of an actin filament The structure of F-actin was determined from X-ray diffraction data and computer model-building. Fourteen actin subunits are shown (all are different colors except the central actin subunit, whose two halves are blue and gray).

Initially, polymerization of actin monomers is slow because actin dimers and trimers are unstable. But once a longer polymer has formed, subunits add to both ends. Addition is usually much more rapid at the (+) end (hence its name) than at the (−) end

Tubulin forms hollow microtubules

Like actin filaments, microtubules are cytoskeletal fibers built from small globular protein subunits. Consequently, they share with actin filaments the ability to assemble and disassemble on a time scale that allows the cell to rapidly change shape in response to external or internal stimuli. Compared to a microtubule, however, an actin filament is a thin and flexible rod. A microtubule is about three times thicker and much more rigid because it is constructed as a hollow tube. Consider the following analogy: A metal rod with the dimensions of a pencil is easily bent. The same quantity of metal, fashioned into a hollow tube with a larger diameter but the same length, is much more resistant to bending.

Each intermediate filament subunit contains a stretch of α helix flanked by nonhelical regions at the N- and C-termini. Two of these polypeptides interact in register (parallel and with ends aligned) to form a coiled coil. The dimers then associate in a staggered antiparallel arrangement to form higher-order fibrous structures (Fig. 5.28). The fully assembled intermediate filament may consist of 16 to 32 polypeptides in cross-section. Note that no nucleotides are required for intermediate filament assembly. The N- and C-terminal domains may help align subunits during polymerization and interact with proteins that cross-link intermediate filaments to other cell components. Keratin fibers themselves are cross-linked through disulfide bonds between cysteine residues on adjacent chains.

Model of an intermediate filament Pairs of polypeptides form coiled coils. These dimers associate to form tetramers and so on, ultimately producing an intermediate filament composed of 16 to 32 polypeptides in cross-section. Although drawn as straight rods here, the intermediate filament and its component structures are probably all twisted around each other in some way, much like a man-made rope or cable.

Actin filament treadmilling

Net assembly at one end balances net dissociation at the other end. The original segment (darker color) appears to travel along the filament during treadmilling.

The paclitaxel-tubulin interaction appears to include close contacts between paclitaxel's phenyl groups and hydrophobic residues such as phenylalanine, valine, and leucine. Paclitaxel was originally extracted from the slow-growing and endangered Pacific yew tree, but it can also be purified from more renewable sources or chemically synthesized. Paclitaxel is used as an anticancer agent because it blocks cell division and is therefore toxic to rapidly dividing cells such as tumor cells.

Paclitaxel binds to β-tubulin subunits in a microtubule, but not to free tubulin, so it stabilizes the microtubule, preventing its depolymerization.

An animal hair—for example, sheep's wool or the hair on your head—consists almost entirely of keratin filaments (Fig. 5.29). Hair resists deformation but can be stretched. Tensile stress breaks the hydrogen bonds between carbonyl and amino groups four residues apart in the keratin α helix. The helices can then be pulled until the polypeptides are fully extended. Additional force causes the polypeptide chain to break. If unbroken, the protein can spring back—at least partially—to its original α-helical conformation when the force is removed. This is why a wool sweater stretched out of shape gradually reverts to its former style.

Perhaps due to their cable-like construction, intermediate filaments undergo less remodeling than cellular fibers constructed from globular subunits such as actin and tubulin. For example, nuclear lamins disassemble and reassemble only once during the cell cycle, when the cell divides. Keratins, as part of dead cells, remain intact for years. In the innermost layers of animal skin, epidermal cells synthesize large amounts of keratin. As layers of cells move outward and die, their keratin molecules are pushed together to form a strong waterproof coating. Because keratin is so important for the integrity of the epidermis, mutations in keratin genes are linked to certain skin disorders. In diseases such as epidermolysis bullosa simplex (EBS), cells rupture when subject to normal mechanical stress. The result is separation of epidermal layers, which leads to blistering. The most severe cases of the disease arise from mutations in the most highly conserved regions of the keratin molecules, near the ends of the α-helical regions.

Intermediate filament proteins as a group are much more heterogeneous than the highly conserved actin and tubulin. For example, humans have about 65 intermediate filament genes. The lamins are the intermediate filaments that help form the nuclear lamina in animal cells, a 30-100-Å-thick network inside the nuclear membrane that helps define the nuclear shape and may play a role in DNA replication and transcription. In many cells, intermediate filaments are much more abundant than actin filaments or microtubules and are most prominent in the dead remnants of epidermal cells—that is, in the hard outer layers of the skin—where they may account for 85% of the total protein (Fig. 5.25). The best-known intermediate filament proteins are the keratins, a large group of proteins that include the "soft" keratins, which help define internal body structures, and the "hard" keratins of skin, hair, and claws.

Scanning electron micrograph of sectioned human skin The layers of dead epidermal cells at the top consist mostly of keratin.

Bicycle frames, plant stems, and bones are built on this same principle. Cells use hollow microtubules 1. to reinforce other elements of the cytoskeleton (see Fig. 5.14) 2. to construct cilia and flagella 3. to align and separate pairs of chromosomes during mitosis.

The basic structural unit of a microtubule is the protein tubulin. Two monomers, known as α-tubulin and β-tubulin, form a dimer, and a microtubule grows by the addition of tubulin dimers. Each tubulin monomer contains about 450 amino acids, 40% of them identical in α- and β-tubulin. The core of tubulin consists of a four-stranded and a six-stranded β sheet surrounded by 12 α helices image is beta tubulin = The strands of the two β sheets are shown in blue, and the 12 α helices that surround them are green.

The collagen triple helix is stabilized through hydrogen bonding. One set of interactions links the backbone N─H group of each glycine residue to a backbone C=O group in another chain.

The geometry of the triple helix prevents the other backbone N─H and C═H groups from forming hydrogen bonds with each other, but they are able to interact with a highly ordered network of water molecules surrounding the triple helix like a sheath.

Capping, branching, and severing proteins, along with other proteins whose activity is sensitive to extracellular signals, regulate the assembly and disassembly of actin filaments. A cell containing a network of actin filaments can therefore change its shape as the filaments lengthen in one area and regress in another. Certain cells use this system to move. When a cell crawls along a surface, actin polymerization extends its "leading" edge, while depolymerization helps retract its "trailing" edge (Fig. 5.19a).

The high density of growing filament ends at the leading edge of the cell (Fig. 5.19b) illustrates how the rapid formation and outward extension of actin filaments can modulate cell shape and drive cell locomotion. Not only do actin filaments provide structural support and generate cell movement by assembly and disassembly, they also participate in generating tensile force. This system is well developed in muscle cells, where actin filaments are an essential part of the contractile apparatus (see Section 5.4).

cytoskeleton

The network of intracellular fibers that gives a cell its shape and structural rigidity.

Actin polymerization is driven by the hydrolysis of ATP (splitting ATP by the addition of water) to produce ADP + inorganic phosphate (Pi):

This reaction is catalyzed by F-actin but not by G-actin. Consequently, most of the actin subunits in a filament contain bound ADP. Only the most recently added subunits still contain ATP. Because ATP-actin and ADP-actin assume slightly different conformations, proteins that interact with actin filaments may be able to distinguish rapidly polymerizing (ATP-rich) actin filaments from longer-established (ADP-rich) actin filaments.

Each tubulin subunit includes a nucleotide-binding site. Unlike actin, tubulin binds a guanine nucleotide, either guanosine triphosphate (GTP) or its hydrolysis product, guanosine diphosphate (GDP). When the dimer forms, the α-tubulin GTP-binding site becomes buried in the interface between the monomers. The nucleotide-binding site in β-tubulin remains exposed to the solvent (Fig. 5.21). After the tubulin dimer is incorporated into a microtubule and another dimer binds on top of it, the β-tubulin nucleotide-binding site is also sequestered from solvent. The GTP is then hydrolyzed, but the resulting GDP remains bound to β-tubulin because it cannot diffuse away (the GTP in the α-tubulin subunit remains where it is and is not hydrolyzed).

The tubulin dimer The guanine nucleotide (gold) in the α-tubulin subunit (bottom) is inaccessible in the dimer, whereas the nucleotide in the β-tubulin subunit (top) is more exposed to the solvent.

extracellular matrix The extracellular proteins and polysaccharides that fill the space between cells and form connective tissue in animals.

There are at least 28 types of collagen with different three-dimensional structures and physiological functions. The most familiar is the collagen from animal bones and tendons, which forms thick, ropelike fibers (Fig. 5.30). This type of collagen is a trimeric molecule about 3000 Å long but only 15 Å wide. As in all forms of collagen, the polypeptide chains have an unusual amino acid composition and an unusual conformation. Except in the extreme N- and C-terminal regions of the polypeptides (which are cleaved off once the protein exits the cell), every third amino acid is glycine, and about 30% of the remaining residues are proline and hydroxyproline (Hyp). Hyp residues result from the hydroxylation of Pro residues after the polypeptide has been synthesized, in a reaction that requires ascorbate (vitamin C; Box 5.B).

Three views of a coiled coil

These models show a segment of the coiled coil from the protein tropomyosin. (a) Backbone model. (b) Stick model. (c) Space-filling model. Each α-helical chain contains 100 residues. The nonpolar strips along each helix contact each other, so the two helices wind around each other in a gentle left-handed coil.

Distribution of cytoskeletal fibers in a single cell

To make these micrographs, each type of fiber was labeled with a fluorescent probe that binds specifically to one type of cytoskeletal protein. Note how the distribution of actin filaments differs somewhat from that of intermediate filaments and microtubules.

Collagen is a triple helix

Unicellular organisms can get by with just a cytoskeleton, but multicellular animals must have a way to hold their cells together according to some characteristic body plan. Large animals—especially nonaquatic ones—must also support the body's weight. This support is provided by collagen, which is the most abundant animal protein. It plays a major structural role in the extracellular matrix (the material that helps hold cells together), in connective tissue within and between organs, and in bone. Its name was derived from the French word for glue (at a time when glue was derived from animal connective tissue).

Polymerized actin is sometimes referred to as F-actin (for filamentous actin, to distinguish it from G-actin, the globular monomeric form). The actin polymer is actually a double chain of subunits in which each subunit contacts four neighboring subunits (Fig. 5.16). Each actin subunit has the same orientation (for example, all the nucleotide-binding sites point up in Fig. 5.16), so the assembled fiber has a distinct polarity. The end with the ATP site is known as the (−) end, and the opposite end is the (+) end.

f-actin = The polymerized form of the protein actin. See also G-actin. g-actin = The monomeric form of the protein actin. See also F-actin. (-) end = The end of a polymeric filament where growth is slower. See also (+) end. (+) end = The end of a polymeric filament where growth is faster. See

For a stretch of about 1000 residues, each collagen chain consists of repeating triplets, the most common of which is Gly-Pro-Hyp. Glycine residues, which have only a hydrogen atom for a side chain, can normally adopt a wide range of secondary structures. However, the imino groups of proline and hydroxyproline residues (that is, their connected side chains and amino groups) constrain the geometry of the peptide group. The most stable conformation for a polypeptide sequence containing repeating units of Gly-Pro-Hyp is a narrow left-handed helix

imino groups Collagen structure (a) A sequence of repeating Gly-Pro-Hyp residues adopts a secondary structure in which the polypeptide forms a narrow left-handed helix. The residues in this stick model are color-coded: Gly gray, Pro orange, Hyp red. H atoms are not shown. (b) Space-filling model of a single collagen polypeptide. (c) Space-filling model of the triple helix. (d) Backbone trace showing the three polypeptides in different shades of gray. Each polypeptide has a left-handed twist, but the triple helix has a right-handed twist.

The importance of collagen for the structure and function of connective tissues means that irregularities in the collagen protein itself or in the enzymes that process collagen molecules can lead to serious physical abnormalities. Hundreds of collagen-related mutations have been identified. Because most tissues contain more than one type of collagen, the physiological manifestations of collagen mutations are highly variable. Defects in collagen type I (the major form in bones and tendons) cause the congenital disease osteogenesis imperfecta. The primary symptoms of the disease include bone fragility leading to easy fracture, long-bone deformation, and abnormalities of the skin and teeth.

osteogenesis imperfecta A disease caused by mutations in collagen genes and characterized by bone fragility and deformation. Collagen type I, a trimeric molecule, contains two different types of polypeptide chains. Therefore, the severity of the disease depends in part on whether one or two chains in a collagen molecule are affected. Furthermore, the location and nature of the mutation determine whether the abnormal collagen retains some normal function. For example, in one severe form of osteogenesis imperfecta, a 599-base deletion in a collagen gene represents the loss of a large portion of triple helix. The resulting protein is unstable and is degraded intracellularly. Milder cases of osteogenesis imperfecta result from amino acid substitutions, for example, the replacement of glycine by a bulkier residue. Other amino acid changes may slow intracellular processing and excretion of collagen polypeptides, which affects the assembly of collagen fibers. Osteogenesis imperfecta affects about one in 10,000 people.

The basic structural unit of an intermediate filament is a dimer of α helices that wind around each other—that is, a coiled coil. The amino acid sequence in such a structure consists of seven-residue repeating units in which the first and fourth residues are predominantly nonpolar. In an α helix, these nonpolar residues line up along one side (Fig. 5.26). Because a nonpolar group appears on average every 3.5 residues but there are 3.6 residues per α-helical turn, the strip of nonpolar residues actually winds slightly around the surface of the helix. Two helices whose nonpolar strips contact each other therefore adopt a coiled structure with a left-handed twist

this is a coiled coil Arrangement of residues in a coiled coil This view down the axis of two seven-residue α helices shows that amino acids at positions 1 and 4 line up on one side of each helix. Nonpolar residues occupying these positions form a hydrophobic strip along the sides of the helices.

Actin filaments continuously extend and retract Actin filaments are dynamic structures. Polymerization of actin monomers is a reversible process, so the polymer undergoes constant shrinking and growing as subunits add to and dissociate from one or both ends of the microfilament (see Fig. 5.17). When the net rate of addition of subunits to one end of an actin filament matches the net rate of removal of subunits at the other end, the polymer is said to be treadmilling (Fig. 5.18).

treadmilling = The addition of monomeric units to one end of a polymer and their removal from the opposite end such that the length of the polymer remains unchanged.