BIOCHEMISTRY TOPIC 5: PROTEIN FOLDING AND LEVELS OF PROTEIN STRUCTURE

Which of the following best describes the nature of protein primary structure? Structural elements such as alpha helices and beta pleated sheets Amino acids linked together in a specific order by peptide bonds Two or more polypeptide chains coming together to form the final functional protein The overall three-dimensional shape of a chain of amino acids

Amino acids linked together in a specific order by peptide bonds The sequence of amino acids connected by peptide bonds in a specific order defines protein primary structure. "Structural elements such as alpha helices and beta pleated sheets" refers to secondary structure. "The overall three-dimensional shape of a chain of amino acids" refers to tertiary structure. "Two or more polypeptide chains coming together to form the final functional protein" refers to quaternary structure.

Primary structure consists of the order of ______ in a protein. These are held together with ______ bonds that are formed by a ______ reaction. Nucleotides, phosphodiester, dehydration Amino acids, peptide, hydrolysis Amino acids, peptide, dehydration Nucleotides, peptide, dehydration

Amino acids, peptide, dehydration Protein primary structure is defined by the order of amino acids that make up the protein. The amino acids are linked together by peptide bonds, which are formed via dehydration reactions. Dehydration reactions involve two molecules reacting to produce H2O and another product molecule. These reactions are called dehydration reactions because it is as if the two reactant molecules were dehydrated (H2O was removed from them).

In order to fulfill their function, proteins must fold in proper, three-dimensional conformations. Which one of the following molecules, available in a cell, is likely to help a protein fold properly? Cysteine Glycine Chaperone Polymerase

Chaperones are proteins that bind newly-made polypeptides and enable proper folding. Chaperones also bind to misfolded proteins to help them fold back into their proper shapes. Ensuring proper protein folding is vital because proteins that do not fold properly—often due to genetic mutations that substitute one amino acid for another—can lead to a variety of diseases.

Which type of bonding or interaction is correctly paired with a chemical or change in environment that will disrupt/break the interaction or bond? Peptide bonds: Reducing agents Hydrophobic interactions: Change in pH Peptide bonds: Change in pH Hydrogen bonds/ionic bonds: Change in pH

Correct answer Hydrogen bonds/ionic bonds: Change in pH The correct answer is "Hydrogen bonds/ionic bonds: Change in pH." If you chose "Peptide bonds: Reducing agents:" Reducing agents can break disulfide bonds, but not peptide bonds. Peptide bonds are broken by special digestive enzymes, such as pepsin and trypsin. If you chose "Hydrophobic interactions: Change in pH:" Nonpolar amino acid sidechains contain nonpolar bonds that do not favorably interact with ions such as H+, which varies with changes in pH. Changes in pH instead disrupt hydrogen bonds and ionic bonds, whereas hydrophobic interactions may be disrupted by heat. If you chose "Peptide bonds: Change in pH:" Peptide bonds will not be affected by changes in pH. Peptide bonds are broken by special digestive enzymes, such as pepsin and trypsin. Changes in pH instead disrupt hydrogen bonds and ionic bonds.

A patient presents with a fever of 110°F. Which interaction(s) would be disrupted within a neuronal protein if the fever isnʼt resolved quickly. Hydrogen Bond Disulfide Bond Hydrophobic Interactions Ionic Bonds

Correct answer Hydrophobic Interactions The patient's temperature is much higher than normal. High temperatures disrupt hydrophobic interactions. If you chose "Hydrogen Bonds:" Hydrogen bonds are stronger interactions than hydrophobic interactions and will not be easily disrupted by heat as hydrophobic interactions will. Hydrogen bonds are disrupted by changes in pH and by increasing the concentration of salts in the protein's environment. If you chose "Disulfide Bonds:" Disulfide bonds are strong interactions that will not be easily disrupted by heat. Disulfide bonds are disrupted by reacting with reducing agents. If you chose "Ionic Bonds:" Ionic bonds are strong interactions that will not be easily disrupted by heat. Ionic bonds are disrupted by changes in pH and by increasing the concentration of salts in the protein's environment.

Which of the following statements about the different levels of protein structure is true? Two or more polypeptides each with their own secondary structures come together to form a single larger tertiary structure of a protein Peptide bonds between amino acids make up the secondary structure of a protein The interactions between the side chains of the amino acids make up the secondary level structure of a protein The interactions between the side chains of the amino acids make up the tertiary level structure of a protein

Correct answer The interactions between the side chains of the amino acids make up the tertiary level structure of a protein If you chose "Two or more polypeptides each with their own secondary structures come together to form a single larger tertiary structure of a protein:" Two or more polypeptides each with their own tertiary structures come together to form a single larger quaternary structure of a protein. If you chose "Peptide bonds between amino acids make up the secondary structure of a protein:" Peptide bonds between amino acids make up the primary structure of a protein. If you chose "The interactions between the side chains of the amino acids make up the secondary level structure of a protein:" The hydrogen bonding between backbone atoms in a protein make up its secondary structure, whereas the interactions between the side chains of the amino acids make up the tertiary level structure of a protein.

Which of the following forces can lead to aggregation as a result of protein misfolding? disulfide bonds hydrogen bonds ionic bonds hydrophobic interactions

Correct answer hydrophobic interactions Misfolded proteins can have sections of hydrophobic amino acid residues exposed to water. This can lead to misfolded proteins to aggregate in order to form favorable hydrophobic interactions between nonpolar amino acids in adjacent protein chains and to keep these hydrophobic residues away from water. If you chose "Disulfide bonds:" While a disulfide bond could form between two cysteines on different protein chains, cysteines are frequently already participating in a disulfide bond inside of the protein chain or are bonded to something like a metal. The likelihood of two protein chains forming a cysteine bond randomly is very low. If you chose "Hydrogen bonds:" Hydrogen bonds can form between polar amino acid side-chains and water, so there is no driving force for polar amino acids to form hydrogen bonds specifically with other polar amino acids on other proteins. If you chose "Ionic bonds:" Charged amino acid side-chains can interact favorably with water as well as with other charged amino acid side-chains (of opposite charge). There is no strong driving force for charged amino acids to form ionic bonds specifically with other polar amino acids on other proteins.

Describe the role of a chaperone protein.

Correct answer A chaperone protein helps other proteins to fold into their correct, functional shapes (i.e. attain their native folds). Just as a chaperone escorts younger people to an event and helps keep them out of trouble, a chaperone protein helps proteins to maintain their normal shapes and avoid aggregation, i.e. stay out of trouble!

A diabetic patient is suffering from ketoacidosis. Which interaction(s) could be disrupted within the patientʼs hemoglobin due to this condition. (Click all that apply) Hydrogen Bond Disulfide Bond Hydrophobic Interactions Ionic Bonds

Correct answer Hydrogen Bond Ionic Bonds Diabetic ketoacidosis leads to a lower pH than normal. Changes in pH can disrupt both hydrogen bonds and ionic bonds inside of a protein. If you chose "Disulfide bonds:" Disulfide bonds are disrupted by reducing agents. If you chose "Hydrophobic interactions:" Hydrophobic interactions are not affected by changes in pH, but are disrupted by increases in temperature (heating). If you chose either "Hydrogen Bonds" or "Ionic Bonds" but not both, you are partially correct! Both types of interactions can be disrupted by changes in pH.

What types of bonds primarily hold together the secondary structure of a protein?

Correct answer Hydrogen bonds between protein backbone atoms lead to protein secondary structure

Which of the following statements about protein structure and stability is true? Denaturation is the loss of primary, secondary, and tertiary structure Denatured proteins retain their tertiary structure Ionic bonds between the side chains of the charged amino acids stabilize the protein structure Protein structure is not stabilized by the hydrophobic effect

Correct answer Ionic bonds between the side chains of the charged amino acids stabilize the protein structure The true statement is "Ionic bonds between the side chains of the charged amino acids stabilize the protein structure." Ionic bonds help stabilize both the tertiary structure of a protein chain and the quaternary structure of a protein with multiple subunits. If you chose "Denaturation is the loss of primary, secondary, and tertiary structure:" When a protein is denatured, all levels of structure except for primary are lost. If you chose "Denatured proteins retain their tertiary structure:" Proteins that have been denatured retain all of their peptide bonds, which determines their primary structure, but all other levels of protein structure are lost. If you chose "Protein structure is not stabilized by the hydrophobic effect:" The largest force governing protein structure is the hydrophobic effect, which causes hydrophobic R groups to cluster together in the interior of a protein in order to minimize their contact with water. This arrangement stabilizes the folded polypeptide backbone, since unfolding it or extending it would expose the hydrophobic R groups to water.

Which of the following statements about the secondary structure of proteins is true? You may select more than one answer. It involves hydrogen bonding between the backbone atoms. It includes alpha helices as a common form. It includes beta pleated sheets as a common form. It involves hydrogen bonding between amino acid side-chains.

Correct answer It involves hydrogen bonding between the backbone atoms. It includes alpha helices as a common form. It includes beta pleated sheets as a common form. Secondary structures arise from hydrogen bonding patterns between backbone atoms. The most common secondary structures are alpha-helices and beta sheets. Hydrogen bonding between side-chains contributes to protein tertiary structure, but not secondary structure. If you chose one or more of the three marked options above, you are partially correct!

Which of the following are true about a misfolded protein? You may select more than one answer. It will lose its normal function. It can be degraded by the cell. It can be the result of denaturation. It can cause protein aggregation. It loses its primary structure.

Correct answer It will lose its normal function. It can be degraded by the cell. It can be the result of denaturation. It can cause protein aggregation. he following options are correct: "It will lose its normal function:" The function of a protein is heavily dependent on its three-dimensional shape. As a protein misfolds changes in three-dimensional shape lead the protein to lose its ability to perform its normal function. "It can be degraded by the cell:" In addition to chaperone proteins being able to help misfolded protein refold, the cell also has mechanisms for identifying and breaking down misfolded proteins into amino acids to prevent these misfolded proteins from forming aggregates. "It can be the result of denaturation:" Denaturation disrupts side chain interactions, which destabilizes tertiary structure and can cause the protein to change shape, i.e. misfold. "It can cause protein aggregation:" Misfolded proteins can have sections of hydrophobic amino acid residues exposed to water. This can lead to misfolded proteins to aggregate in order to keep these hydrophobic residues away from water. If you chose some of the above, you are partially correct! If you chose "It loses its primary structure:" This is incorrect because the primary structure is determined by the peptide bonds between amino acids in the protein, which are strong covalent bonds that are not broken by the protein changing shape or from conditions which cause the protein to denature.

What types of bonds are used to generate the primary structure of a protein?

Correct answer Peptide bonds between amino acids lead to a protein's primary structure.

What is the name for the level of protein structure when two or more polypeptide chains interact with one another? Secondary Primary Tertiary Quaternary

Correct answer Quaternary Quaternary structure is formed when two or more protein chains with developed tertiary structures interact through their side-chains. If you chose "Secondary:" Secondary structure is formed when backbone atoms in a peptide chain form hydrogen bonds and leads to alpha helices and beta sheets. If you chose "Primary:" Primary structure involves the sequence of amino acids in a peptide chain, linked by peptide bonds. If you chose "Tertiary:" Tertiary structure involves the final, three-dimensional shape of a single peptide chain.

Intracellular, extracellular, and intercellular spaces are composed of water. How does that affect protein structure?

Correct answer The structure of proteins will tend to be such that the interactions between nonpolar amino acid residues, which are hydrophobic, and water are minimized (i.e. the hydrophobic effect). Thus, the nonpolar amino acids of proteins will tend to remain in protein interiors. Since polar and charged amino acids can interact favorably with water or each other, the hydrophobic effect is the major determining factor in a protein's final structure.

Which of the following interactions involve a covalent bond? (check all that apply) peptide bond hydrogen bond hydrophobic interaction ionic bond disulfide bond

Correct answer peptide bond disulfide bond A covalent bond is a bond between to atoms involving the electrons being shared between them. In proteins, these include peptide bonds and disulfide bonds. If you chose "Hydrogen bond:" A hydrogen bond is not a covalent bond; rather, it may be considered to be significantly weaker version of an ionic bond. There is no sharing of electrons between the two groups participating in a hydrogen bond. Instead, they are attracted to each other by opposite partial charges on an H atom and an O/N atom (or S in the case of cysteine). If you chose "Hydrophobic interaction:" Hydrophobic interactions are very weak attractive forces between two non-polar groups, and do not involve the formation of covalent bonds between the two groups. If you chose "Ionic bond:" There is no sharing of electrons between the two groups participating in an ionic bond. Instead, they are attracted to each other by opposite charges on the two sidechains. If you chose either "Peptide bond" or "Disulfide bond" but not both, you are partially correct! Both of the above are covalent bonds.

The negatively charged amino acid, Glutamate, is replaced with the negatively charged amino acid Aspartate. Which level of protein structure is most significantly impacted by this change? primary structure secondary structure tertiary structure quaternary structure

Correct answer primary structure The original and substitute amino acid both have a negative charge and can both form an ionic bond with a positively charge amino acid. If you chose "tertiary structure or quaternary structure:" Contributions to quaternary and tertiary structure, which are dependent on side-chain interactions, are most likely unaffected as both aspartate and glutamate can form ionic bonds with positively charged amino acid side chains. If you chose "secondary structure:" The secondary structure of a protein depends on backbone interactions, and these are probably unaffected. The amino acid sequence, however, has been altered, and so the primary structure has certainly been changed.

Define Disulfide bonding

Correct answer Disulfide bonding involves the formation of a covalent bond between the S atoms of two cysteine amino acid residues in a protein

Define Hydrogen bonding

Correct answer Hydrogen bonding is an attraction between an H atom in a polarized bond with an O, N, or S atom and another O, N, or S atom. It may be thought of as a very weak version of an ionic bond, with the H atom having a partial positive charge and the O, N, or S atom having a partial negative charge.

Explain the relative strength of the forces that stabilize protein structure.

Correct answer Hydrophobic interactions, on a singular basis, are the weakest of the four forces. However, the driving force of hydrophobic species to avoid water (the hydrophobic effect) is the key determining factor in a protein taking on its final structure. Hydrogen bonds are stronger than hydrophobic interactions, but since these may be formed between polar amino acid side chains or between side chains and water hydrogen bonds are not a major determining factor in a protein's tertiary structure, but rather help to "tweak" it. Ionic and disulfide bonds are the strongest side chain interactions, but also serve to "tweak" a protein's structure

What is the difference between tertiary and quaternary structure?.

Correct answer Tertiary structure refers to the three-dimensional shape of a peptide chain. All proteins have tertiary structure. Quaternary structure refers to two or more peptide chains, called subunits, closely associating with one another in a specific way to form the functional protein. Only proteins made up of more than one protein chain have quaternary structure.

Which parts of the amino acids in the primary structure interact to form the secondary structure?.

Correct answer The O=C-N-H atoms that make up the peptide bonds in the protein's backbone (i.e. the atoms that are not part of amino acid side-chains) hydrogen bond with one another to form the protein secondary structure.

Differentiate between the hydrophobic effect and hydrophobic interactions.

Correct answer The hydrophobic effect is the migration of nonpolar amino acid residues of a protein into the protein's interior so as to minimize unfavorable interactions with water, which remains on the exterior of the protein. Hydrophobic interactions are weak attractions between the R groups of nonpolar amino acid residues.

What type of reaction breaks peptide bonds apart? Condensation Reaction Methylation Reaction Hydrolysis Reaction Oxidation/Reduction Reaction

Hydrolysis Reaction Peptide bonds are formed by dehydration reactions (named for the loss of water that occurs) and broken via hydrolysis (named for the addition of water: "hydro-" meaning water, and "-lysis" meaning cutting, i.e. water cuts the peptide bond).

Frying an egg in a pan changes the egg white color from translucent to white. Which interaction(s) would be disrupted within the Ovalbumin protein? Hydrogen Bond Disulfide Bond Hydrophobic Interactions Ionic Bonds

Hydrophobic Interactions Just as protein structure is stabilized primarily by the hydrophobic effect and hydrophobic interactions, disruption of hydrophobic interactions is the simplest way to denature a protein. This is generally done by applying heat. High temperatures cause the atoms in a protein to move so quickly that the structure loosens and causes the hydrophobic core to open up and expose the nonpolar residues to water.

As a piece of bacon is heated in a skillet on the stove, you observe that the appearance of the bacon changes. You may even notice that the bacon becomes crispy if left in the skillet. What type of bonds or interactions in proteins are susceptible to temperature changes? Ionic Bonds Hydrogen Bonds Hydrophobic interactions Disulfide Bonds

Hydrophobic interactions Just as protein structure is stabilized primarily by the hydrophobic effect and hydrophobic interactions, disruption of hydrophobic interactions is the simplest way to denature a protein. This is generally done by applying heat. High temperatures cause the atoms in a protein to move so quickly that the structure loosens and causes the hydrophobic core to open up and expose the nonpolar residues to water. If you chose "Ionic Bonds:" Ionic bonds are strong interactions that will not be easily disrupted by heat. Ionic bonds are disrupted by changes in pH and by increasing the concentration of salts in the protein's environment. If you chose "Hydrogen Bonds:" Hydrogen bonds are stronger interactions than hydrophobic interactions and will not be easily disrupted by heat as hydrophobic interactions will. Hydrogen bonds are disrupted by changes in pH and by increasing the concentration of salts in the protein's environment. If you chose "Disulfide Bonds:" Disulfide bonds are strong interactions that will not be easily disrupted by heat. Disulfide bonds are disrupted by reacting with reducing agents.

Define Ionic bonding

Ionic bonding occurs when two oppositely charged species, or ions, are attracted to one another and remain in close proximity. In protein tertiary and quaternary structure, ionic bonding occurs between negatively charged R groups (aspartate and glutamate) and positively charge R groups (lysine and arginine). Note that two ions with charges of the same sign will repel one another, and not form an ionic bond.

Several types of side chain interactions stabilize the tertiary structure of proteins, including which of the following? Hydrogen bonds, phosphodiester bonds, peptide bonds, covalent bonds Ionic bonds, peptide bonds, protein bonds, hydrogen bonds. Ionic bonds, hydrophobic interactions, hydrogen bonds, disulfide bonds Peptide bonds, hydrogen bonds, ester bonds, covalent bonds

Ionic bonds, hydrophobic interactions, hydrogen bonds, and disulfide bonds are all types of side-chain interactions that contribute to a protein's tertiary structure.

Explain how misfolded proteins are normally dealt with in our cells.

Misfolded proteins are normally dealt with in one of two ways: Either a chaperone protein finds the misfolded protein and helps it to achieve its native fold, or the misfolded protein is broken down by a series of enzymes into its constituent amino acids so that they may be recycled into new proteins.

What type of bond is responsible for the primary structure of a protein? Peptide Bond Hydrogen Bond Glycosidic Bond Ionic Bond

Peptide Bond Protein primary structure is defined by the order of amino acids that make up the protein. The amino acids are linked together by peptide bonds, which are formed via dehydration reactions.

A toddler mistakenly swallows a bathroom cleaning solution, containing a strong reducing agent. Which interaction is most likely to be disrupted within a glycoprotein in the lining of the toddlerʼs esophagus? Hydrogen Bond Disulfide Bond Hydrophobic interactions Ionic Bonds

Reducing agents disrupt disulfide bonds.

When secondary structural elements in one polypeptide chain interact with one another, what is the name for this level of protein structure? Primary Secondary Tertiary Quaternary

Tertiary Secondary structural elements moving and interacting with one another leads the final shape of the protein chain, its tertiary structure, to form.

Which level of protein structure provides all enzymes with their substrate specificity? Primary Secondary Tertiary Quaternary

Tertiary The tertiary (i.e. three-dimensional) structure of an enzyme provides the enzyme's active site with its unique shape, charges, hydrophobic regions, and hydrogen bonding regions that determines its substrate specificity.

Why is the amino acid sequence - the primary structure - so important for a protein's final structure?.

The number of nonpolar, polar, and charged amino acids and their order within the protein chain have a significant affect on what the final three-dimensional structure (the tertiary structure) a given protein will be. The sequence of the amino acids can also have an effect on which secondary structural elements form in which parts of the protein.

Some proteins can have more than one stable conformation. Is this beneficial or detrimental? Explain.

Unfortunately, the presence of more than one stable conformation can often prove to detrimental: One of the conformations could have the correct shape and number of exposed hydrophobic amino acid residues to promote aggregation, leading to large, insoluble fibers that can kill cells. This is particularly an issue in the brain and is the cause of diseases such as Alzheimer's disease and Parkinson's disease, among others.

In a chain of amino acids held together by peptide bonds, the N-terminal and C-terminal amino acids have their characteristic physiological charge. Why have the other amino acids in the chain lost this characteristic?

When a peptide bond is formed between two amino acids, the charged species from the carboxyl group of one amino acid and the amino group of the other amino acid combine to form water. Once the peptide bond is formed, the groups which created the peptide bond and water do not carry charges.