4.1 Molecular Structure of Proteins

What does the tertiary structure determine?

It determines the function because it is the three-dimensional shape of the molecule that enables the protein to serve as structural support, membrane, channel, enzyme, or signaling molecule

What does the primary structure determine, other than the amino acid sequence?

It determines the second and tertiary structure

Amino Group

NH2; a nitrogen atom bonded to two hydrogen atoms. an amino group is present covalently linked to the central carbon atom of an amino acid.

What groups bind in the tertiary structure?

R groups

What happens if the pH is in the range of 7.35-7.45 (physiological pH--slightly basic)?

The amino group gains a proton to become NH3 and the carboxyl group loses a proton to become COO

Draw one of the 20 amino acids and label the amino group, the carboxyl group, and R group (side chain), and the α carbon.

The carboxyl group and the α carbon are the same for all amino acids. The amino group is the same for almost all the amino acids, with proline being the exception. The variety of functions and forms among the amino acids is mainly due to their different side chains (R groups). See Figure 4.2.

What ultimately determines the three-dimensional shape of a protein?

The order of amino acids in the polypeptide chain determines the way in which proteins fold because of the various interactions and bonds formed between amino acids. These interactions, depending on the type and location, will give rise to specific secondary and tertiary structures.

A mutation leads to a change in one amino acid in a protein. The result is that the protein no longer functions properly. How is this possible?

The sequence of amino acids in a protein determines how a protein folds, so a change in even a single amino acid can affect the way the protein folds and can disrupts its function. For example, if the hydrophobic R groups of two amino acids must aggregate for proper structure and function, then a mutation that changes one of the hydrophobic amino acids to an acidic or a basic amino acid will prevent this aggregation and disrupt structure and function. Similarly, if proper folding requires interaction between the R groups of an acidic and a basic amino acid, then changing either one of them to a hydrophobic amino acid means that proper folding will not take place.

How many amino acids are commonly found in proteins?

20

How many amino acids are in a complete turn of of an alpha helix?

3.6

The fully folded structure of a functional protein composed of a single polypeptide chain is referred to as: A) tertiary B) quaternary C) secondary D) primary

A) tertiary

How do hydrophilic and hydrophobic amino acids interact with one another?

Hydrophobic interact with hydrophobic (via Van der Waals) forces and hydrophilic interact with hydrophilic

Where do hydrogen bonds form in alpha helices?

every fourth amino acid

How are amino acids read?

groups of three or one-letter abbreviations from the amino end to the carboxyl end

Residue

in the context of protein synthesis, any of the amino acids that is incorporated into a protein

Where are hydrophobic amino acids usually located?

in the interior of folded proteins, where they do not interact with water

What are proteins?

linear polymers of any combination of 20 amino acids

What are the ends of an amino acid?

one end is the amino end with a free amino group and one end is the carboxyl end with a free carboxyl group

How does hydrogen bonding occur in the polypeptide backbone?

the carbonyl group in one peptide bond and the amid group in another form hydrogen bonds that allow localized regions of the polypeptide chain to fold

α (alpha) carbon

the central carbon atom of each amino acid

Amino End

the end of a polypeptide chain that has a free amino group

Carboxyl End

the end of a polypeptide chain that has a free carboxyl group

Protein

the key structural and functional molecules that do the work of the cell, providing structural support and catalyzing chemical reactions. the term "protein" is often used as a synonym for "polypeptide"

What determines a protein's shape and function?

the order of amino acids

What is the impact of the R groups projecting outward in an alpha helix?

the outward facing R groups determine where the alpha helix is positioned in the folded protein based on whether its hydrophilic or hydrophobic

Tertiary Structure

the overall three-dimensional shape of a protein, formed by interactions between secondary structures

What is the structure of a Beta sheet?

the polypeptide folds back and forth on itself, forming a pleated sheet that is stabilized by hydrogen bonds between carbonyl groups in one chain and amide groups in another. the antiparallel configuration is more stable because the carbonyl group and amide group are more optimally positioned for hydrogen bonding

Primary Structure

the sequence of amino acids in a protein

Secondary Structure

the structure formed by interactions between stretches of amino acids in a protein

Quaternary Structure

the structure that results from the interactions of several polypeptide chains

Denature

the unfolding of proteins by chemical treatment or high temperature; the separation of paired, complementary strands of nucleic acids

Carboxyl Group

COOH; a carbon atom with a double bond to oxygen and a single bond to a hydroxyl group

The unfolding of a protein by heat or chemical treatment is referred to as: A) depolymerization B) disaggregation C) hydrolysis D) denaturation E) uncoupling

D) denaturation

The interactions between amino acids are major factors in determining the shape of a protein. These interactions can be affected by the environment surrounding a protein. Which factor would have an effect on the shape of a protein? A) the pH of the environment B) whether the other molecules in the environment are predominantly hydrophilic or hydrophobic C) the concentrations of ions present in the environment D) the temperature of the environment E) All of these choices are correct

E) All of these choices are correct

What shape does an amino acid form?

Four covalent bonds from the alpha carbon are at equal angles, forming a tetrahedron, a pyramid with four triangular faces

What are the three "special" amino acids?

Glycine, Proline, and Cysteine

What makes glycine unique?

-the R group is hydrogen (like the other hydrogen group), creating a symmetrical shape (as opposed to asymmetrical) -nonpolar and small enough to tuck into spaces where other R groups would not fit -the small size allows for more rotation around the C-N bond since its R group does not get in the way of the R groups of neighboring amino acids -overall, increases the flexibility of the polypeptide backbone, which can be important in the folding of the protein

What makes proline unique?

-the R group links back to the amino group (NH) -the linkage back creates a kink or bend in the polypeptide chain and restricts the rotation of the C-N bond, imposing constraints on protein folding in its vicinity, an effect that is opposite of glycine

What makes cysteine unique?

-the SH group contributes to protein folding -two cysteine side chains can form an S-S disulfide bond, which covalently binds joins the side chains, which is stronger than the ionic interaction -this can create a cross-bridge that can connect different parts of the same protein or even different proteins, which contributes to the overall structure of single proteins or combinations of proteins

What are the three models to display protein folding?

1) Ball and Stick Model (draws attention to atoms in an amino acid) 2) Ribbon Model (emphasizes secondary structures depicted as alpha helices and beta sheets) 3) Space Filling Model (shows the overall shape and contour of the folded protein)

What is the general structure of an amino acid?

1) a central carbon atom (alpha carbon) that is connected by covalent bonds to four different chemical groups 2) amino group (NH2) 3) a carboxyl group (COOH) 4) a hydrogen atom 5) a variable side chain or R group

What are the three major groups of amino acids as categorized by the properties of their R groups? How do the chemical properties of each group affect protein shape?

Amino acids can be categorized into three major groups based on the properties of their side chains. The first group consists of the hydrophobic ("water-fearing") amino acids, whose side chains are nonpolar, usually found buried in the interior of the folded proteins, and typically form bonds with other hydrophobic amino acids (For example, valine) or solvents. The second group consists of the hydrophilic ("water-loving") amino acids. Hydrophilic amino acids include ones with polar side chains, usually found on the outside surface of folded proteins, and typically form bonds with other hydrophilic amino acids or water. Hydrophilic amino acids also include basic amino acids with side chains that are positively charged at intracellular pH (for example, lysine), and acidic amino acids with side chains that are negatively charged (for example, aspartic acid). The third group includes "special" amino acids whose structures and chemical properties have significant effect on higher levels of protein structure because they allow more or less flexibility around the peptide bond (glycine and proline), or allow covalent interactions between side chains (cysteine).

How does the pH of the environment influence amino acids?

At the pH of a cell, the R groups of the basic amino acids gain a proton and become positively charged, whereas those of the acidic amino acids lose a proton and become negatively charged.

Most proteins retain metabolic activity when denatured. A) True B) False

B) False

Proteins that prevent inappropriate folding of newly synthesized proteins are called: A) enzymes B) chaperones C) ribosomes D) polymerases E) synthetases

B) chaperones

Carbonyl group

C=O

Amide group

CO=NH2

How do peptide bonds, hydrogen bonds, ionic bonds, disulfide bridges, and noncovalent interactions (van der Waals forces and the hydrophobic effect) define a protein's four levels of structure?

The way in which amino acids interact and bond in a polypeptide chain is important for the structure and function of the protein. Peptide bonds are important in maintaining the primary structure of a polypeptide chain. These bonds form between the carboxyl group of one amino acid and the amino group of the next amino acid in the chain. Note that these bonds are typically found between amino acid residues in the polypeptide. Hydrogen bonds are important in maintaining the secondary structure of the polypeptide chain. These bonds form between the oxygen in the carbonyl group (C=O) of one peptide bond and the hydrogen in the amid group (NH) of another. This allows regions of the polypeptide to interact with each other and enables the polypeptide to fold. Two common types of secondary structure formed by hydrogen bonding are a helices and B sheets. In terms of secondary structure, these bonds are found between groups in the polypeptide backbone (see Figure 4.5 and 4.6). Four groups of bonds or interactions are important in creating tertiary and quaternary structure. The first group is the ionic bonds that form between a negative charge and a positive charge. For example, an ionic bond would form between a basic amino acid and an acidic amino acid because they have oppositely charges die chains, these bonds can occur between amino acids that are located far apart in the polypeptide chain, thus creating loops and bends in the overall structure the second group comprises the hydrogen bonds that form between the oxygen of one amino acid's side chain and the hydrogen of another amino acid's side chain. The third group consists of the disulfide bridges. These covalent bonds form between two cysteine residues in the same polypeptide chain, or between two cysteines in two different chains. Note that when discussing tertiary structure, these bonds are found between different side chains. The fourth group important to maintaining tertiary and quaternary structure is noncovalent interactions, which include van der Waals forces and hydrophobic interactions that maintain interactions with different domains of the protein and result in a protein's specific shape.

What is the effect of a protein folding slowly?

Their hydrophobic groups are exposed to other macromolecules in the crowded cytoplasm. the hydrophobic effect, along with van der Waals interactions, tends to bring the exposed hydrophobic groups together, and their inappropriate aggregation may prevent proper folding correctly

How does a chaperone operate?

They bind with hydrophobic groups and nonpolar R groups to shield them from inappropriate aggregation, and in repeated cycles of binding and release they give the polypeptide time to find its correct shape

How do hydrophilic molecules bind with one another?

Via ionic bonds

Do amino acids differ in their chemical and physical properties?

Yes

R Group

a chemical group attached to the central carbon atom of an amino acid, whose structure and composition determine the identity of the amino acid; also known as a side chain

Side Chain

a chemical group attached to the central carbon atom of an amino acid, whose structure and composition determine the identity of the amino acid; also known as an R group

Peptide Bond

a covalent bond that links the carbon atom in the carboxyl group of one amino acid to the nitrogen atom in the amino group of another amino acid

Polypeptide

a polymer of amino acids connected by peptide bonds