Chapter 4: Protein Structure and Function

Question 1

Protein Conformation

Answer 1

Precise, three-dimensional shape of a protein or other macromolecule, based on the spatial location of its atoms in relation to one another.

Question 2

Residue

Answer 2

an individual amino acid, a single molecular unit (monomer) within a polymer

Question 3

Protein Side Chain

Answer 3

Portion of an amino acid not involved in forming peptide bonds; its chemical identity gives each amino acid unique properties.

Question 4

Protein Backbone

Answer 4

Repeating sequence of the atoms (–N–C–C–) that form the core of a protein molecule and to which the amino acid side chains are attached.

Question 5

N-Terminus and C-Terminus

Answer 5

C-Terminus: The end of a polypeptide chain that carries a free carboxyl group (–COOH)

N-Terminus: The end of a polypeptide chain that carries a free α-amino group.​

Question 6

Peptide

Answer 6

Covalent chemical bond between the carbonyl group of one amino acid and the amino group of a second amino acid containing two or more amino acids.

Question 7

Transmembrane Protein

Answer 7

Membrane protein that extends through the lipid bilayer, with part of its mass on either side of the membrane. Protein that cross the lipid bilayer usually form an α helix, composed largely of amino acids with nonpolar side chains

Question 8

What is primary structure? What determines primary structure?

Answer 8

The primary structure of a polypeptide is determined by it’s sequence of amino acids. The unique sequence of amino acids in a protein is called the primary structure of that protein, and only cosists of peptide bonds and amino acids.

Question 9

On the DIPEPTIDE, label the following: Two central carbons, N-term, C-term, two R groups

Answer 9

Question 10

What is secondary structure?

• What are the two major types of secondary structure?
• What type of bond is found in secondary structure?
• Are R groups involved with secondary structure?

Answer 10

-A secondary structure is a local conformations induced by hydrogen bonding along the peptide backbone. Regular local folding pattern of a polymeric molecule. In proteins, it refers to α helices and β sheets.

-One type is alpha helix is a folding pattern, common in many proteins,

in which a single polypeptide chain twists around itself to form a rigid cylinder stabilized by

hydrogen bonds between every fourth amino acid. Another type is Folding pattern found in many proteins in which neighboring regions of the polypeptide chain associate side-by-side with each other through hydrogen bonds to give a rigid and, flattened structure.

-hydrogen bonds that form between the N–H and C=O groups in the polypeptide backbone​

-R groups are involved with secondary structure as side chains.

Question 11

What is tertiary structure?

What types of bonds are found in tertiary structure?

Are R groups involved with tertiary structure?

Answer 11

-Complete three-dimensional structure of a fully folded protein, and is formed due to the interactions between the R-groups.

-Bonds found in a tertiary structure are a covalent bond such as that of a disulfide bond of covalent linkages containg chains of cysteines

-R-groups are what give rise to the structure of the teritary structure due to the side chains, keeping the shape unique from side interactions.

Question 12

What is quaternary structure?

Answer 12

Complete structure formed by multiple, interacting polypeptide chains that form a larger protein molecule that contain two or more amino acids in a linked bond.

Question 13

Define the following:

Dimer:

Trimer:

Tetramer:

Subunit:

Homotrimer:

Heterotetramer:

Protein Domain:

Protein Family:

Ligand:

Allosteric:

Answer 13

Dimer: A chemical compound composed of two identical or similar (not necessarily identical) subunits or monomers.​

Trimer: A chemical compound that is composed of a polymer comprising three monomer units.

Tetramer: A chemical compound that is composed of a polymer comprising four monomer units

Subunit: A monomer that forms part of a larger molecule, such as an amino acid residue in a protein or a nucleotide residue in a nucleic acid. Can also refer to a complete molecule that forms part of a larger molecule. Many proteins, for example, are composed of multiple polypeptide chains, each of which is called a protein subunit.​

Homotrimer: A trimer , especially a biologically active one, derived from three identical monomers.​

Heterotetramer: is protein containing four non-covalently bound subunits, wherein the subunits are not all identical. A homotetramer contains four identical subunits.​

Protein Domain: Segment of a polypeptide chain that can fold into a compact, stable structure and that often carries out a specific function.​

Protein Family: A group of polypeptides that share a similar amino acid sequence or three-dimensional structure, reflecting a common evolutionary origin. Individual members often have related but distinct functions, such as kinases that phosphorylate different target proteins.​

Ligand: General term for a small molecule that binds to a specific site on a macromolecule.

Allosteric: Describes a protein that can exist in multiple conformations depending on the binding of a molecule (ligand) at a site other than the catalytic site; such changes from one conformation to another often alter the protein’s activity or ligand affinity.

Question 14

How do proteins interact with ligands? (What holds them together?)

Answer 14

The ability of a protein to bind selectively and with high affinity to a ligand is due to the formation of a set of weak, noncovalent interactions—hydrogen bonds, electrostatic attractions, and van der Waals attractions—plus favorable hydrophobic forces. Each individual noncovalent interaction is weak, so that effective binding requires many such bonds to be formed simultaneously. This is possible only if the surface contours of the ligand molecule fit very closely to the protein, matching it like a hand in a glove

Question 15

What are the FOUR ways that protein function is regulated (function turned ON/OFF). Explain each.

Answer 15

1. Some proteins are regulated by the non-covalent binding of small molecules, such as amino acids or nucleotides, that cause a change in the conformation and thus, the activity of the protein.
2. Some proteins are regulated by phosphorylation (the addition of phosphate groups) of specific amino acids on the protein. Since phosphorylation is reversible, this process serves as a handy on-off switch.
3. Some proteins are regulated by interactions among the polypeptides making up the protein, or between the protein and other proteins in the cell.
4. Some proteins are regulated by enzymes that is controlled through digestion of a particular ion or macromolecule to break it down.

Question 16

How many different amino acids are commonly used in making proteins?

Answer 16

*Proteins are made from a set of 20 common amino acids. Therefore, a protein that is n amino acids long has 20n different possible sequences.*

20

Question 17

Which parts of amino acids are involved in a peptide bond?

Answer 17

*The peptide bond is formed between the nitrogen atom of the amino group of one amino acid and the carbon atom of the carboxyl group of another amino acid.*

amino group of one amino acid and carboxyl group of the other

Question 18

What is the best type of model for visualizing the surface of a protein?

Answer 18

*The space-filling model is the best type of model for visualizing the surface of a protein. This model provides a contour map of a protein’s surface, which reveals which amino acids are exposed on the surface and shows how the protein might look compared to a small molecule such as water or to another macromolecule in the cell.*

Space-filling model

Question 19

What are the two types of β sheets?

Answer 19

*The two types of β sheets are parallel and antiparallel. 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.*

parallel and antiparallel

Question 20

What does the primary structure of a protein refer to?

Answer 20

*The primary structure of a protein refers to the linear amino acid sequence of the protein.
The chain of linear polymers of amino acids that compose proteins is termed a polypeptide. The primary structure determines the secondary and tertiary structures.*

the linear amino acid sequence of the protein

Question 21

Consider the thermodynamic properties of chemical reactions. Even though enzymes do not affect the overall energy of the reactants or the products (i.e., the thermodynamics), they alter the speed of the reaction. Enzymes accomplish this by doing which of the following?

Answer 21

*Enzymes reduce the activation energy of a reaction. The activation energy is an energy barrier to reactions. For a colliding water molecule to break a bond linking two sugars, the polysaccharide molecule has to be distorted into a particular shape—the transition state—in which the atoms around the bond have an altered geometry and electron distribution. Conditions are thereby created in the microenvironment of the enzyme-active site that greatly reduce the activation energy necessary for the hydrolysis to take place.*

reducing the activation energy of a reaction

Question 22

For a given protein, hydrogen bonds can form between which of the following?

A. atoms in the polypeptide backbone

B. atoms of two peptide bonds

C. atoms in two side chains

D. a side chain and water

E. all of the above

F. none of the above

Answer 22

*For a given protein, hydrogen bonds can form between atoms in the polypeptide backbone, between atoms of two peptide bonds, between atoms in two side chains, and also between a side chain and water. The ability of a protein to bind selectively and with high affinity to a ligand is due to the formation of a set of weak, noncovalent interactions—hydrogen bonds. *

E.

Question 23

How does an allosteric inhibitor work?

Answer 23

*To regulate enzyme activity, an allosteric inhibitor binds to a second site, causing a conformational change in the enzyme that makes the active site less accommodating to the substrate. Unlike competitive inhibition, allosteric inhibition cannot be overcome by experimentally elevating the concentration of the substrate. With allosteric inhibition, there is no direct competition between inhibitor and substrate as both molecules are binding to the enzyme at different locations. There is also no direct interaction between the product of an enzyme and allosteric inhibition of that enzyme. Instead, products from reactions later in the pathway are more likely to act as inhibitors.*

It binds to a site other than the active site, causing a conformational change in the enzyme that makes the active site less accommodating to the substrate.

Question 24

How does phosphorylation control protein activity?

Answer 24

* Proteins are commonly controlled by phosphorylation and dephosphorylation. When added to the protein, the phosphate group induces a change in the protein’s conformation. Regulation of protein activity in this manner involves attaching a phosphate group covalently to one or more of the protein’s amino acid side chains. *

The phosphate group induces a change in the protein’s conformation.

Question 25

What kind of enzyme adds a phosphate group to another protein?

Answer 25

* Protein phosphorylation involves the enzyme-catalyzed transfer of the terminal phosphate group of ATP to the hydroxyl group on a serine, threonine, or tyrosine side chain of the protein. This reaction is catalyzed by a protein kinase. The reverse reaction—removal of the phosphate group, or dephosphorylation—is catalyzed by a protein phosphatase.*

Kinase

Question 26

What kind of enzyme removes a phosphate group from a protein?

Answer 26

*Protein phosphorylation involves the enzyme-catalyzed transfer of the terminal phosphate group of ATP to the hydroxyl group on a serine, threonine, or tyrosine side chain of the protein. This reaction is catalyzed by a protein kinase. However, the reverse reaction—removal of the phosphate group, or dephosphorylation—is catalyzed by a protein phosphatase.*

phosphatase​

Question 27

In an α helix, hydrogen bonds form between which of the following?

Answer 27

*In an α helix, hydrogen bonds form between every fourth amino acid. An α helix is generated when a single polypeptide chain turns around itself to form a structurally rigid cylinder. *

every fourth amino acid

Question 28

Sort the category

[α helix only]

[β sheet only]

[Both α helix & β sheet]

• Side chains alternating above and below the structure
• One full turn every 3.6 amino acids
• Cylindrical structure
• Can be formed by many sequences
• Consists of antiparallel or parallel strands
• Formed by hydrogen-bonding between backbone atoms

Answer 28

Question 29

Predict what would happen to the secondary structure of a protein if an alcohol that disrupts hydrogen-bonding were added.

Answer 29

*Both α helices and β sheets result from hydrogen bonding of backbone atoms within the protein. Disrupting hydrogen bonding will cause both structures to unfold.*

The β sheets would unfold, disrupting protein structure. The α helices would unfold, disrupting protein structure.

Question 30

This antibody is composed of ____ polypeptide chains.

Answer 30

*This antibody is composed of four polypeptide chains. There are two heavy chains and two light chains. *

Four

Question 31

If SDS-PAGE were used for a pure sample of this protein that was preincubated with mercaptoethanol, then there would be ___ bands expected.

Answer 31

*If SDS-PAGE were used for a pure sample of this protein that was exposed to mercaptoethanol, then there would be two bands expected. This is because mercaptoethanol reduces disulfide bonds, so the heavy chains will all co-migrate and the light chains will all co-migrate a bit faster.*

Two

Question 32

How do most motor proteins ensure their movements are unidirectional?

Answer 32

*To achieve such directionality, one of the steps must be made irreversible. For proteins that are able to move in a single direction for long distances, this irreversibility is achieved by coupling one of the conformational changes to the hydrolysis of an ATP molecule that is tightly bound to the protein—which is why motor proteins are also ATPases. A great deal of free energy is released when ATP is hydrolyzed, making it very unlikely that the protein will undergo a reverse shape change, as required for moving backward. Such a reversal would require that the ATP hydrolysis be reversed by adding a phosphate molecule to ADP to form ATP. As a consequence, the protein moves steadily forward, not backward.*

They couple a conformational change to the hydrolysis of an ATP molecule.

Question 33

A disulfide bond is a(n) ___ interaction within the protein.

Answer 33

*The disulfide bond is a covalent interaction within the protein. Disulfide bonds help stabilize a favored protein conformation. Covalent disulfide bonds form between adjacent cysteine side chains by a reaction between their polar –SH groups. These disulfide bonds (also called S–S bonds) are formed, before a protein is secreted, by an enzyme in the endoplasmic reticulum that links together two –SH groups from cysteine side chains that are adjacent in the folded protein. Disulfide bonds do not change a protein’s conformation, but instead act as a sort of “atomic staple” to reinforce the protein’s most favored conformation. The disulfide bond is a covalent interaction within the protein. Disulfide bonds help stabilize a favored protein conformation. Covalent disulfide bonds form between adjacent cysteine side chains by a reaction between their polar –SH groups.*

Covalent

Question 34

Answer 34

*Disulfide bonds form by oxidation and resolve by reduction. Disulfide bonds generally do not form in the cell cytosol, where a high concentration of reducing agents converts such bonds back to cysteine –SH groups. Apparently, proteins do not require this type of structural reinforcement in the relatively mild conditions inside the cell. The oxidation of the thiol group (loss of electrons) causes the new bond formation between both sulfur atoms. When the reduction takes place, electrons are donated back to the bond, thereby allowing hydrogen ion association and reversion back to the thiol. Disulfide bonds form by oxidation and resolve by reduction. Disulfide bonds generally do not form in the cell cytosol, where a high concentration of reducing agents converts such bonds back to cysteine –SH groups. The oxidation of the thiol group (loss of electrons) causes the new bond formation between both sulfur atoms.*

Question 35

Answer 35

*The three-dimensional structure of proteins is commonly represented in four different ways, each of which emphasizes different features of the protein. The backbone model shows the overall organization of the polypeptide chain and provides a straightforward way to compare the structures of related proteins. The ribbon model shows the polypeptide backbone in a way that emphasizes its most conspicuous folding patterns. The wire model includes the positions of all the amino acid side chains; this view is especially useful for predicting which amino acids might be involved in the protein’s activity. Finally, the space-filling model provides a contour map of the protein surface, which reveals which amino acids are exposed on the surface and shows how the protein might look to a small molecule (such as water) or to another macromolecule in the cell.*

Question 36

Protein molecules that have a quaternary structure must have two or more of which of the following?

Answer 36

*Protein molecules that have a quaternary structure must have two or more polypeptide chains. If a protein molecule exists as a complex of more than one polypeptide chain, then these interacting polypeptides form its quaternary structure. Though proteins with quaternary structure may have a variety of features (including extensive secondary structures, disulfide bonds, antigen binding sites, and domains), these do not define this level of protein structure. Proteins with quaternary structure are composed of more than one polypeptide chain, and therefore have multiple N- (and C-) termini. *

polypeptide chains

Question 37

What is the definition of a protein-binding site?

Answer 37

*A protein-binding site is any region on a protein’s surface that interacts with another molecule through noncovalent bonding. A protein can contain binding sites for a variety of molecules, large and small. If a binding site recognizes the surface of a second protein, the tight binding of two folded polypeptide chains at this site will create a larger protein, whose quaternary structure has a precisely defined geometry. Covalent bonding is not involved in the idea of a protein-binding site.*

any region on a protein’s surface that interacts with another molecule through noncovalent bonding

Question 38

What are protein families?

Answer 38

*Protein families are evolutionarily related proteins that are similar in amino acid sequence and three-dimensional conformation. Serine proteases are great examples of proteins that are classified in the same protein family. Once a protein has evolved a stable conformation with useful properties, its structure can be modified over time to enable it to perform new functions. We know that this occurred quite often during evolution because many present-day proteins can be grouped into protein families, in which each family member has an amino acid sequence and a three-dimensional conformation that closely resemble those of the other family members. Some portions of their amino acid sequences are found to be nearly the same. The similarity of their three-dimensional conformations is even more striking: most of the detailed twists and turns in their polypeptide chains, which are several hundred amino acids long, are virtually identical.*

evolutionarily related proteins that are similar in amino acid sequence and three-dimensional conformation

Question 39

In a globular protein, where would the amino acid tryptophan most likely be found?

Answer 39

*In a globular protein, the amino acid tryptophan would most likely be found buried in the interior of the protein. Nonpolar, hydrophobic amino acids, such as tryptophan, tend to cluster in the interior of the folded protein to avoid contact with the aqueous cytosol. Hydrophobic forces help proteins fold into compact conformations. In a folded protein, polar amino acid side chains tend to be displayed on the surface, where they can interact with water; nonpolar amino acid side chains are buried inside the protein to form a tightly packed hydrophobic core of atoms that are hidden from water.*

buried in the protein’s interior

Question 40

What does the primary structure of a protein refer to?

Answer 40

*Because a protein’s structure begins with its amino acid sequence, this is considered its primary structure. That is, the primary structure of a protein refers to the linear amino acid sequence of the protein. The chain of linear polymers of amino acids that compose proteins is termed a polypeptide. The locations of the peptide bonds that form the protein’s backbone are between each of the amino acids of the protein. The peptide bonds are involved in maintaining primary structure, but the location of the peptide bonds does not specify the primary structure. The primary structure does determine the secondary and tertiary structures.*

the linear amino acid sequence of the protein

Question 41

What do the segments of a transmembrane protein that cross the lipid bilayer usually consist of?

Answer 41

*The segments of a transmembrane protein that cross the lipid bilayer usually consist of an α helix with mostly nonpolar side chains. There is a wide array of different membrane-bound proteins and many of them cross the lipid bilayer as an α helix. The hydrophobic side chains of the amino acids that form the helix make contact with the hydrophobic hydrocarbon tails of the phospholipid molecules, while the hydrophilic parts of the polypeptide backbone form hydrogen bonds with one another along the interior of the helix. About 19–21 amino acids are required to span a membrane in this way.*

an α helix with mostly nonpolar side chains

Question 42

For which reason are α helices and β sheets common folding patterns in polypeptides?

Answer 42

*α helices and β sheets are such common folding patterns in polypeptides because the amino acid side chains are not directly involved in their formation. Both of these folding patterns result from hydrogen bonds that form between N–H groups and C=O groups along the polypeptide backbone. The hydrogen of the amino hydrogen is partially positively charged and the oxygen of the carbonyl is partially negatively charged. Because amino acid side chains are not directly involved in forming these hydrogen bonds, α helices and β sheets can be formed by many different amino acid sequences.*

The amino acid side chains are not directly involved in their formation.

Question 43

A protein can be unfolded by a process called ___

Answer 43

*A protein can be unfolded by a process called denaturing. A protein can be unfolded, or denatured, by treatment with solvents that disrupt the noncovalent interactions holding the folded chain together. This treatment converts the protein into a flexible polypeptide chain that has lost its natural shape. Oxidation, reduction, and aggregation are not the best terms for this unfolding process.*

denaturation

Question 44

Generally speaking, what determines the biological activity of a protein?

Answer 44

*In general, the biological activity of a protein is determined by its amino acid sequence. Each type of protein has a particular three-dimensional structure, which is determined by the order of the amino acids in its polypeptide chain. The ability to form α helices and/or β sheets is not generally involved in the biological activity of a protein. In other words, all proteins are different, and some contain α helices and/or β sheets while others do not. Even though all proteins are different, all contain peptide bonds and hydrogen bonds to varying degrees. *

amino acid sequence

Question 45

What provides the information necessary to specify the three-dimensional shape of a protein? Choose the best answer in the context of which generally applies to most proteins.

Answer 45

*A protein’s amino acid sequence provides the information necessary to specify the three-dimensional shape of a protein. The ordering of amino acids is what allows some amino acids to interact noncovalently with other amino acids when the protein begins to fold. Each type of protein has a particular three-dimensional structure, which is determined by the order of amino acids in its polypeptide chain. The final folded structure, or conformation, adopted by any polypeptide chain is determined by energetic considerations: a protein generally folds into the shape in which its free energy (G) is minimized. The folding process is thus energetically favorable, as it releases heat and increases the disorder of the universe. Peptide bonds are important in keeping amino acids bonded together and the protein intact, but the peptide bond does not provide the information necessary to specify the protein’s three-dimensional shape. Though interactions with other polypeptides and chaperones can be important for protein function, these interactions also do not specifically provide the information for a protein’s three-dimensional shape. Urea destabilizes protein structure. A protein can be unfolded, or denatured, by treatment with solvents like urea that disrupt the noncovalent interactions holding the folded chain together.*

protein’s amino acid sequence

Question 46

Which part of an amino acid gives it its unique properties?

Answer 46

*The side chain of an amino acid is what gives the amino acid its unique chemical properties; the side chain is sometimes also called the R-group. All 20 naturally occurring amino acids are identical except in the collections of atoms composing these side chains.

Each amino acid contains an amino group (consisting of nitrogen and hydrogen atoms) and a carboxyl group (consisting of carbon, oxygen, and hydrogen atoms) that are covalently bonded to an α-carbon. The side chain is also covalently bonded to the α-carbon. Individual amino acids of all types are covalently linked together into a linear polypeptide by the peptide bond, which is formed between the amino and carboxyl groups of neighboring amino acids.*

side chain

Question 47

Which parts of amino acids are involved in a peptide bond?

Answer 47

*The peptide bond always comprises both a nitrogen atom and a carbon atom, where the nitrogen atom from the amino group and the carbon atom from the carboxyl group undergo a condensation reaction and eliminate a water molecule in the process. The amino acid side chains do not participate in the peptide bond, meaning that all types of amino acids can form peptide bonds with all other types. *

amino group of one amino acid and carboxyl group of the other

Question 48

Hydrogen bonding between N–H and C=O groups of every fourth amino acid within a polypeptide chain results in which type of folding pattern?

Answer 48

*The hydrogen bonds that form a ß-pleated sheet structure occur between the N–H and C=O groups of amino acids in different segments of a single polypeptide chain lying side by side. Amyloid structures are ß sheets that interlock with each other through their side chains. The α helices are formed by hydrogen bonds between every fourth amino acid in the primary structure.*

Question 49

A stretch of amino acids in a polypeptide chain that is capable of independently folding into a defined structure is called a

Answer 49

*A domain is a sequence of amino acids in a polypeptide chain that adopts a defined folding pattern based on the interactions of the side chains, as well as contributions from the polypeptide backbone molecules. This is distinct from a subunit, which is a term used for a single, complete polypeptide chain that can interact with other subunits to form a larger complex.*

domain

Question 50

A binding site on the surface of a protein interacts specifically with another protein through

Answer 50

*Covalent interactions are rarely used between protein molecules because they are difficult to break, often requiring an enzyme. Interactions between proteins and their partners need to be reversible but very specific. A specific interaction, but one that is able to be altered, can be achieved through formation of many weak noncovalent interactions between proteins and their binding partners.*

many weak noncovalent interactions.

Question 51

How does phosphorylation of a protein affect its activity?

Answer 51

*Phosphorylation of amino acid side chains in a protein changes their charge to a negative charge. It could lead to changes in conformation of the protein, differences in binding to partners, and either increased or decreased activity of an enzyme. Thus, the effects of protein phosphorylation are particular to the protein itself.*

could increase or decrease activity

Question 52

Shown here is the ATP hydrolysis cycle of a motor protein. What sentence BEST describes the state of the motor protein in “C”?

Answer 52

*(A) is the state where no ATP or ADP is bound. The protein is bound to the filament with one of its two filament-binding domains, while the other binding domain is unbound. (B) shows that upon ATP binding, a conformational change moves the unbound domain forward one step to interact with the filament. In (C), ATP is hydrolyzed to ADP, creating a conformational change to release the rear filament-binding domain and bring it forward.*

The hydrolysis of ATP to ADP caused a conformational change in the protein.