The Shape and Structure of Proteins // Chapter 4 // BIO115

Many protein molecules contain multiple copies of the same protein subunit.

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Proteins come in a variety of shapes and sizes.

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Ribbon models show three different protein domains.

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Protein conformation can be represented in a variety of ways.

-backbone model -ribbon model -wire model -space-filling model

Three types of noncovalent bonds help proteins fold.

-electrostatic attractions -hydrogen bond -van der Waals attractions Although a single one of these bonds is quite weak, many of them together can create a strong bonding arrangement that stabilizes a particular three-dimensional structure.

β-sheets come in two varieties.

1.) Antiparallel β-sheet 2.) Parallel β-sheet Both of these structures are common in proteins.

Collagen and elastin are abundant extracellular fibrous proteins.

A collagen molecule is a triple helix formed by three extended protein chains that wrap around one another. Many rodlike collagen molecules are cross-linked together in the extracellular space to form collagen fibrils, which have the tensile strength of steel. The striping on the collagen fibril is caused by the regular repeating arrangement of the collagen molecules within the fibril. Elastin molecules are cross-linked together by covalent bonds to from rubberlike, elastic fibers. Each elastin polypeptide chain uncoils into a more extended conformation when the fiber is stretched, and recoils spontaneously as soon as the stretching force is relaxed.

Amino acids are linked together by peptide bonds.

A covalent peptide bond forms when the carbon atom of the carboxyl group of one amino acid shares electrons with the nitrogen atom from the amino group of a second amino acid. Because a molecule of water is eliminated, peptide bond formation is classified as a condensation reaction.

The helix is a common, regular, biological structure.

A helix will form when a series of similar subunits bind to each other in a regular way. A helix can either be right-handed or left-handed.

Identical protein subunits can assemble into complex structures.

A protein with just one binding site can form a dimer with another identical protein. Identical proteins with two different binding sites will often form a long, helical filament. If the two binding sites are disposed appropriately in relation to each other, the protein subunits will form a closed ring instead of a helix.

A protein is made of amino acids linked together into a polypeptide chain.

The amino acids are linked by peptide bonds to form a polypeptide backbone of repeating structure, from which the side chain of each amino acid projects. The character and sequence of the chemically distinct chains give each protein its distinct, individual properties. Proteins are typically made up of chains of several hundred amino acids, whose sequence is always presented starting with the N-terminus reading from left to right.

Chaperone proteins can guide the folding of a newly synthesized polypeptide chain.

The chaperones bind to newly synthesized or partially folded chains and helping them to fold along the most energetically favorable pathway. Association of these chaperones with the target protein requires an input of energy from ATP hydrolysis.

Many viral capsids are more or less spherical protein assemblies.

They are formed from many copies of a small set of protein subunits. The nucleic acid of the virus (DNA or RNA) is packaged inside.

Denatured proteins can often recover their natural shapes.

This type of experiment demonstrates that the conformation of a protein is determined solely by its amino acid sequence. Renaturation requires the correct conditions and works best for small proteins.

Prion diseases are caused by proteins whose misfolding is infectious.

The protein undergoes a rare conformational change to give an abnormally folded prion. The abnormal form causes the conversion of normal proteins in the host's brain into a misfolded prion form.

Twenty different amino acids are commonly found in proteins.

There are equal numbers of polar (hydrophilic) and non polar (hydrophobic) side chains, and half of the polar side chains carry a positive or negative charge.

Stacking of β-sheets allows some misfiled proteins to aggregate into amyloid fibers.

( amyloid fibers---insoluble protein aggregates that include those associated with neurodegenerative disorders, such as Alzheimer's disease and prion diseases. )

Serine proteases constitute a family of proteolytic enzymes.

( serine proteases-- a family of protein-cleaving (proteolytic) enzymes that includes the digestive enzymes chymotrypsin, trypsin, and elastase as well as several proteases involved in blood clotting. ) Serine proteases derive their name from the amino acid serine.

A single type of protein subunit can pack together to form a filament, a hollow tube, or a spherical shell.

Actin subunits, for example, form actin filaments, whereas tubular subunits form hollow microtubules, and some virus proteins form a spherical shell that encloses the viral genome.

Disulfide bonds help stabilize a favored protein conformation.

Covalent disulfide bonds form between adjacent cysteine side chains by the oxidation of their -SH groups. These cross-links can join either two parts of the same polypeptide chain or two different polypeptide chains. Because the energy required to break one covalent bond is much larger than the energy required to break even a whole set of noncovalent bonds, a disulfide bond can have a major stabilizing effect on a protein's folded structure.

Many proteins are composed of separate functional domains.

Elements of secondary structures such as α helices and β-sheets pack together into stable, independently folding, globular elements called protein domains. A typical protein molecule is built from one or more domains, linked by a region of polypeptide chain that is often relatively unstructured.

Some proteins are formed as a symmetrical assembly of two different subunits.

Hemoglobin, an oxygen-carrying protein abundant in red blood cells, contains two copies of α-globin and two copies of β-globin. Each of these four polypeptide chains contains a heme molecule, where oxygen is bound. Thus, each molecule of hemoglobin in the blood carries four molecules of oxygen.

Polypeptide chains often fold into one of two orderly repeating forms known as an α-helix and a β-sheet.

In an α-helix, the N-H of every peptide bond is hydrogen-bonded to the C=O of a neighboring peptide bond located four amino acids away in the same chain. In a β-sheet, several segments (strands) of an individual polypeptide chain are held together by hydrogen-bonding between peptide bonds in adjacent strands. The amino acid side chains in each strand project alternately above and below the plane of the sheet.

Other chaperone proteins act as isolation chambers that help a polypeptide fold.

In this case, the barrel of the chaperone provides an enclosed chamber in which a synthesized polypeptide chain can fold without the risk of aggregating with other polypeptides in the crowded conditions of the cytoplasm. This system also requires an input of energy from ATP hydrolysis, mainly for the association and subsequent dissociation of the cap that closes off the chamber.

Hydrogen bonds within a protein molecule help stabilize its folded shape.

Large numbers of hydrogen bonds form between adjacent regions of the folded polypeptide chain. ( note that the same amino acid side chain can make multiple hydrogen bonds )

Hydrophobic forces help proteins fold into compact conformations.

Polar amino acid side chains tend to be displayed on the outside of the folded protein, where they can interact with water; the non polar amino acid side chains are buried on the inside to form a highly packed hydrophobic core of atoms that are hidden from water.

Intertwined α helices can from a stiff coiled-coil.

Proteins that form coiled-coils typically have non polar amino acids. Two α helices can wrap around each other, with the non polar side chain of one α-helix interacting with the non polar side chains of the other, while the more hydrophilic amino acid side chains are left exposed to the aqueous environment.

An actin filament is composed of identical protein subunits.

The helical array of actin molecules in a filament often contains thousands of molecules and extends for micrometers in the cell.

Many membrane-bound proteins cross the lipid bilayer as an α-helix.

The hydrophobic side chains of the amino acids forming the α-helix contact the hydrophobic hydrocarbon tails of the phospholipid molecules, while the hydrophilic parts of the polypeptide backbone form hydrogen bonds with one another in the interior of the helix. About 20 amino acids are required to span a membrane this way.