Protein Structure

• The primary structure of a polymer dictates the sequence of monomers.

Secondary Structure

• Hydrogen bonds are most important in the secondary structure of proteins.
• Structures that repeat in secondary structure are called supersecondary structures.
• Covalent bonds are important in all protein structures except secondary structures.
• Hydrogen bonding in secondary structures can be intrachain in α-helices and either intrachain or interchain in β-sheets.

Tertiary Structure

• The overall folding of a single protein subunit defines its tertiary structure.
• Disulfide bonds and prosthetic group locations are most important in tertiary structure.

Primary Structure Forces

• Covalent bonds are involved in maintaining the primary structure of a protein.
• A single amino acid substitution can lead to a malfunctioning protein.

Alpha Helix

• In a continuous α-helix, the carbonyl oxygen of glutamic acid is hydrogen-bonded to the amide nitrogen of leucine.
• Proline is unlikely to be found in an α-helix due to its cyclic structure.
• Clusters of amino acids with bulky or similarly charged R-groups tend to destabilize α-helices.

Protein Denaturation

• Protein denaturation disrupts the secondary structure while the primary structure remains intact.

Domains

• A domain is a supersecondary region shared by proteins with a specific function.
• A domain refers to independently folded regions of proteins

Collagen

• Collagen structure is best described as a triple helix.
• As an animal ages, the amount of cross-linking of collagen in tissue tends to increase.
• Vitamin C (ascorbic acid) prevents scurvy, because it is used to hydroxylate prolines in the primary structure of collagen.
• Vitamin C is necessary for the synthesis of hydroxyproline, crucial for holding the three strands of collagen together.
• Fibrous proteins can be composed of either helical or β-sheet structures.

Beta sheet

• The peptide bonds in the β-sheet are extended.
• Both α-helices and β-sheets can be found as part of tertiary structure.
• Reverse turns are often found connecting the strands of an antiparallel β-sheet.
• In the β-pleated sheet conformation, hydrogen bonds are perpendicular to the direction of the polypeptide chain, and the polypeptide chains may be hydrogen bonded together in a parallel or antiparallel orientation.

Motifs

• A motif is a repetitive supersecondary structure.

Fibrous Proteins vs Globular Proteins

• The most common function for fibrous proteins is providing structural roles.
• The peptide chain bends back on itself in the alpha-helix, featuring hydrogen bonds parallel to the helix axis.
• Globular proteins tend to be water soluble.

Supersecondary Structures

• The pyrrole ring is not an example of supersecondary structure.

Myoglobin

• The protein myoglobin contains a heme group.
• The structure of myoglobin consists almost entirely of α-helices.
• Myoglobin has a histidine that prevents both O2 and CO from binding perpendicularly to the heme plane, lessening the difference in myoglobin's affinity for CO versus O2.
• The iron atom must be in the 2+ oxidation state (Fe(II)) for heme to bind oxygen.
• The heme group of myoglobin is held in place only through non-covalent bonding.

Protein Properties

• Generally speaking, globular proteins are water-soluble.
• Two amino acids frequently found in reverse turns are glycine and proline.
• Leucine would most likely be found in the interior of a globular protein.
• Disulfide bonds in proteins occur between the side chains of cysteine residues.

Bonding

• Refer to Exhibit 4B: The type of bonding labeled "L" is Hydrogen bonding of the peptide backbone, "O" is Covalent bonding involving the R-groups, and "N" is Electrostatic attraction.
• Refer to Exhibit 4B: M shows hydrogen bonding of R-groups.
• Refer to Exhibit 4B: L shows hydrogen bonding of the peptide backbone.
• Refer to Exhibit 4B: O shows covalent bonding of R-groups.
• Refer to Exhibit 4B: N shows electrostatic attraction of R-groups.

X-Ray Crystallography

• X-ray crystallography helps determine protein structure because the positions of all atoms can be found by this method.

Tertiary Structure Interactions

• The tertiary structure of a protein is usually a result of intramolecular hydrogen bonding, electrostatic interactions, and hydrophobic interactions.

Prosthetic Groups

• Heme is best described as a prosthetic group.

Denaturation

• Protein denaturation can result from heat, extremes of pH, and detergents
• Disulfide bonds, hydrogen bonds, and hydrophobic attraction forces are important in tertiary structure

Quaternary Structure

• Quaternary structure is associated with the relative orientation of one polypeptide to another polypeptide in a multi-subunit protein.
• Hydrogen bonds, ionic interactions, and hydrophobic interactions maintain quaternary structure.

Hemoglobin vs Myoglobin

• Fetal Hb binds oxygen more tightly than adult Hb under normal circumstances.
• Myoglobin displays simple kinetics of binding, while hemoglobin displays cooperativity.
• Hemoglobin contains two different types of subunits, a prosthetic group, is an allosteric enzyme, and transports oxygen.
• Hemoglobin is a tetramer, whereas myoglobin is a single polypeptide chain.

Bohr Effect

• The Bohr effect for oxygen binding states that as the pH goes down, Hb binds oxygen less tightly.

Allosteric Interactions

• In allosteric interactions, changes that take place in one site of a protein cause changes at a distant site.

Hemoglobin and BPG

• The binding of bisphosphoglyceric acid (BPG) to hemoglobin causes oxygen to dissociate from Hb.
• Oxygen binding to hemoglobin is cooperative.
• The binding of oxygen to hemoglobin is decreased by the presence of H+ and CO2.

Fetal Hemoglobin

• The affinity of fetal hemoglobin for oxygen is higher than that of maternal hemoglobin.

Hemoglobin structure

• Variations in the structure of hemoglobin do not always have an adverse effect on health, can alter the binding of heme to the protein, and can occur on the surface of the protein.

Sickle Cell Anemia

• In sickle-cell anemia hemoglobin, groups of hemoglobin molecules aggregate with each other.

Homologous Proteins

• Collagen is not homologous with myoglobin, the α-chain of hemoglobin, or the β-chain of hemoglobin.

Nonpolar Substances

• Increased entropy of solvent water molecules is the major force that drives nonpolar substances out of aqueous solution.

Hydrophobic Interactions

• Hydrophobic interactions may occur between the R groups of phenylalanine and tryptophan.

Protein Structure Info

• Primary structure contains the information needed for the structure of a protein.
• Incorrect protein folding resulting in exposure of hydrophobic regions can result in aggregation.

Chaperones

• Proteins that aid in the correct and timely folding of other proteins are called chaperones.
• Hemoglobin that lacks BPG has an oxygen binding curve closest to that of myoglobin.
• Proline causes a kink or bend in the α-helix.