Biochemistry: A Short Course PDF

Tymoczko Berg Gatto Stryer Biochemistry: A Short Course Fourth Edition CHAPTER 4 Protein Three- Dimensional Structure © 2019 Macmillan Learning Protein Diversity Receptor Why study proteins and their structure? Protein misfolding in health an...

Tymoczko Berg Gatto Stryer Biochemistry: A Short Course Fourth Edition CHAPTER 4 Protein Three- Dimensional Structure © 2019 Macmillan Learning Protein Diversity Receptor Why study proteins and their structure? Protein misfolding in health and disease Salahuddin, P. J Biochem Mol Biol Res 2015. (2): 36-45  Capter 4 : Learning objectives Compare and contrast the different levels of protein structure and how they relate to one another. Describe the biochemical information that determines the final three-dimensional structure of proteins and explain what powers the formation of the structure. Section 4.1 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains Polypeptides consist of amino acids linked by a ___________________. The peptide bond is also called an amide bond. Each amino acid in a protein is called a residue. Diagram of Peptide-Bond Formation  Polypeptide Chains Have Directionality The _________________ end is taken as the beginning of the polypeptide chain, and the __________________ end is the end of the polypeptide chain. The primary structure is always written from the amino terminal to the carboxyl terminal, or left to right.  Backbones of Polypeptide Chains The polypeptide chain consists of a repeating part called the main chain or backbone and a variable part consisting of the distinctive amino acid side chains (R-groups). The backbone has hydrogen-bonding potential because of the carbonyl groups and hydrogen atoms that are bonded to the nitrogen of the amine group. Most proteins have 50 to 2000 amino acids, and the mean molecular weight for an amino acid is 110 g/mol.  Disulfide Bonding of Polypeptide Chains In some proteins, the polypeptide chain can be cross- linked by disulfide bonds. Disulfide bonds form by the ________________ of two cysteines.  Proteins Have Unique Amino Acid Sequences Specified by Genes The complete amino acid sequences of millions of proteins are now known. Figure 4.5 Amino acid sequence of bovine insulin. What is the amino terminus of the tripeptide Gly-Ala- Asp? a. Gly b. Ala c. Asp  Polypeptide Chains Are Flexible Yet Conformationally Restricted The peptide bond is essentially planar. Six atoms (Cα, C, O, N, H, and Cα) lie in a plane. The peptide bond has _________________________ because of _____________; thus, rotation about the bond is prohibited. Model of Planar Peptide Bonds Which statement is false regarding peptide bonds? a. They tend to be planar. b. They are generally in the trans and rarely in the cis configuration. c. They tend to have the amide nitrogen protonated to give a positive charge.  Polypeptide Chains Are Flexible Yet Conformationally Restricted Most peptide bonds are in the trans configuration so as to minimize steric clashes between neighboring R groups. Section 4.2 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Secondary structure is the three-dimensional structure formed by ___________________ between peptide NH and CO groups of amino acids that are near one another in the primary structure. The α helix, β sheets, and turns are prominent examples of secondary structure.  The Alpha Helix Is a Coiled Structure Stabilized by Intrachain Hydrogen Bonds The α helix is a tightly coiled structure, with the R groups bristling out from the axis of the helix. The CO group of each amino acid forms a hydrogen bond with the NH group of the amino acid that is situated four residues ahead in the sequence. All of the backbone CO and NH groups form hydrogen bonds except those at the end of the helix. Essentially all α helices found in proteins are right-handed.  The Hydrogen-Bonding Scheme for an Alpha Helix Destabilized by: - Val, Thr, and Ile (steric clashes - Ser, Asp, and Asn (H-bond donor/acceptor) - Pro (lacks NH group, ring structure prevents bond rotation Model of Ferritin, a Largely Alpha-Helical Protein  Beta Sheets Are Stabilized by Hydrogen Bonding Between Polypeptide Strands The β sheet is another common form of secondary structure. Beta sheets are formed by adjacent β strands. In contrast to an α helix, the polypeptide in a β strand is fully extended.  Beta Sheets Are Stabilized by Hydrogen Bonding Between Polypeptide Strands ___________________ link the strands in a β sheet. The strands of a β sheet may be parallel, antiparallel, or mixed. β sheets may be almost flat or adopt a twisted conformation. Structure of a Mixed Beta Sheet Model of a Twisted Beta Sheet  Polypeptide Chains Can Change Direction by Making Reverse Turns and Loops Turns and loops invariably lie on the surfaces of proteins and thus often participate in interactions between other proteins and the environment.  Fibrous Proteins Provide Structural Support for Cells and Tissues α-Keratin, a structural protein found in wool and hair, is composed of two right-handed α helices intertwined to form a left-handed superhelix called a coiled coil. The helices interact with ionic interactions or van der Waals forces.  Fibrous Proteins Provide Structural Support for Cells and Tissues Collagen is a structural protein that is a component of skin, bone, tendons, cartilage, and teeth. Collagen consists of three intertwined helical polypeptide chains that form a superhelical cable. The helical polypeptide chains of collagen are not α helices.  The Amino Acid Sequence of a Part of a Collagen Chain The helices in collagen are not stabilized by hydrogen bonds. Rather, they are stabilized by __________________ of the pyrrolidine rings of proline. The three intertwined chains interact with one another with hydrogen bonds. What does the primary structure of a protein refer to? a. The presence of cross-links with disulfide bonds. b. The presence of an α-helix. c. The α-amino acid sequence in the polypeptide chain. d. The orientation of the side chains in three-dimensional space. Section 4.3 Tertiary Structure: Water-Soluble Proteins Fold into Compact Structures Tertiary structure refers to the spatial arrangement of amino acids that are far apart in the primary structure and to the pattern of disulfide bond formation. This level of structure is the result of interactions between the R groups of the peptide chain. – Salt bridges – Disulfide bonds  Myoglobin Illustrates the Principles of Tertiary Structure Globular proteins, such as myoglobin, form complicated three-dimensional structures. Globular proteins are very compact. There is little or no empty space in the interior of globular proteins. The interior of globular proteins consists mainly of ________________ amino acids. The exterior of globular proteins consists of ___________ and __________ amino acids. Distribution of Amino Acids in Myoglobin The Three-Dimensional Structure of Myoglobin The Tertiary Structure of Many Proteins Can Be Divided into Structural and Functional Units Motifs, or supersecondary structures, are combinations of secondary structure that are found in many proteins. Some proteins have two or more similar or identical compact structures called domains. Section 4.4 Quaternary Structure: Multiple Polypeptide Chains Can Assemble into a Single Protein Many proteins are composed of multiple polypeptide chains called subunits, or monomers. Such proteins are said to display quaternary structure. Quaternary structure can be as simple as two identical polypeptide chains or as complex as dozens of different polypeptide chains. Model of 2β2 Tetramer of Human Hemoglobin In a typical monomeric protein, which level of structure is most highly conserved? a. Primary structure b. Secondary structure c. Tertiary structure d. Quaternary structure Section 4.5 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure Anfinsen Experiment Urea disrupts ________________________. Mercaptoethanol disrupts ______________________. Diagram of the Role of Beta-mercaptoethanol in Reducing Disulfide Bonds What conditions cause protein denaturation? Diagram for Folding Funnel Model Why is it important to understand protein folding? How does the hydrophobic effect influence protein folding? In an aqueous environment, nonpolar portions of the molecule: a. are generally exposed to solvent and interact effectively with water. b. can be placed on the surface of the molecule only if hydrogen bonded to water. c. are found in the interior of the protein, away from water, which preserves the entropy of water in solution. d. interact with polar portions in the interior of the protein.