fundamentals of biochemistry fourth edition chapter 6 proteins: three-dimensional structure...
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Fundamentals of Biochemistry
Fourth Edition
Chapter 6Proteins: Three-Dimensional Structure
Copyright © 2013 by John Wiley & Sons, Inc. All rights reserved.
Donald Voet • Judith G. Voet • Charlotte W. Pratt
Chapter 6Secondary Structure
Key Concepts 6.1• The planar character of the peptide group limits the conformational flexibility of the polypeptide chain.• The α helix and the β sheet allow the polypeptide chain to adopt favorable φ and ψ angles and to form hydrogen bonds.• Fibrous proteins contain long stretches of regular secondary structure, such as the coiled coils in α keratin and the triple helix in collagen.• Not all polypeptide segments form regular secondary structure such as α helices or β sheets.
Levels of Protein Structure
1° Structure
1° & 2° Structure
1°, 2°, & 3° Structure
1°, 2°, 3° & 4° Structure
Peptide Bonds Assume Trans Conformation
Resonance of Peptide Bond
Extended Conformation of Polypeptide
Torsion Angles of Polypeptide Backbone
Steric Interference ofAdjacent Peptide Groups
Ramachandran Diagram
The α Helix
The α Helix: Space Filling Model
Oxy-MyoglobinPDBid 1A6M
β Sheets
Antiparallel β Sheet
Parallel β Sheet
Pleating of β Sheet
β Sheet: Space Filling Model
Concanavalin APDBid 2CNA
Bovine Carboxypeptidase A
Carboxypeptidase APDBid 3CPA
α-helixβ-sheet
Tertiary Structure
Connecting Adjacent β Strands
A Coiled Coil
Higher Order Structure of α Keratin
Collagen: Triple Helix
Sequence Affects 2º Structure
Chapter 6Tertiary Structure
Key Concepts 6.2 • X-Ray crystallography and NMR spectroscopy are used to determine the positions of atoms in proteins.• Nonpolar residues tend to occur in the protein interior and polar residues on the exterior.• A protein’s tertiary structure consists of secondary structural elements that combine to form motifs and domains.• Over time, a protein’s structure is more highly conserved than its sequence.• Bioinformatics databases store macromolecular structure coordinates. Software makes it possible to visualize proteins and compare their structural features.
Side Chain Location
Oxy-Myoglobin and Concanavalin A PDBids 1A6M and 2CNA
Side Chain Distribution in Cytochrome
Side Chain Distribution in Cytochrome
Side Chain Distribution in Cytochrome
Motifs: Supersecondary Structures
Protein Classification: α, β, or α/β
Cytochrome b562PDBid 256B
Human immunoglobulin fragmentPDBid 7FAB
Dogfish lactate dehydrogenasePDBid 6LDH
Protein Classification: α
Cytochrome b562PDBid 256B
Protein Classification: β
Human immunoglobulin fragmentPDBid 7FAB
Protein Classification: α/β
Dogfish lactate dehydrogenasePDBid 6LDH
Protein Topology: 8-Stranded β Barrels
Human retinol binding proteinPDBid 1RBP
Peptide-N4-(N-acetyl--D-glucosaminyl) asparagine amidasePDBid 1PNG
Triose phosphate isomerasePDBid 1TIM
Protein Topology: 8-Stranded β Barrels
Human retinol binding proteinPDBid 1RBP
Protein Topology: 8-Stranded β Barrels
Peptide-N4-(N-acetyl--D-glucosaminyl) asparagine amidasePDBid 1PNG
Protein Topology: 8-Stranded β Barrels
Triose phosphate isomerasePDBid 1TIM
2-Domain Protein : GAPDH
Glyceraldehyde-3-phosphate dehydrogenasePDBid 1GD1
Structure Conserved More Than Sequence
Internet Bioinformatics Tools
Chapter 6Quaternary Structure & Symmetry
Key Concepts 6.3 • Some proteins contain multiple subunits, usually arranged symmetrically.
4º Structure of Hemoglobin
DeoxyhemoglobinPDBid 2DHB
Chapter 6Protein Stability
Key Concepts 6.4 • Protein stability depends primarily on hydrophobic effects and secondarily on electrostatic interactions.• A protein that has been denatured may undergo renaturation.• Protein structures are flexible and may include unfolded regions.
Hydrophobic & Hydrophilic Tendencies:Hydropathy
Hydropathy Plot:Bovine Chymotrypsinogen
Ion Pairs in Hemoglobin
Metal Ion Stabilized Zinc Finger
DNA-binding protein Zif268PDBid 1ZAA
Chaotropic Agents Denature Proteins
Chapter 6Protein Stability
Checkpoint 6.4• Describe the hydropathic index plot for a fibrous protein such as collagen or keratin.• Describe the forces that stabilize proteins, and rank their relative importance.• Summarize the results of Anfinsen’s experiment with RNase A.• Why would it be advantageous for a protein or a segment of a protein to lack defined secondary or tertiary structure?
Chapter 6Protein Folding
Key Concepts 6.5 • A folding protein follows a pathway from high energy and high entropy to low energy and low entropy.• Protein disulfide isomerase catalyzes disulfide bond formation.• A variety of molecular chaperones assist protein folding via an ATP-dependent bind-and-release mechanism.• Amyloid diseases result from protein misfolding.• The misfolded proteins form fibrils containing extensive β structure.
Hypothetical Protein Folding Pathway
Energy-Entropy Diagram:Protein Folding Funnel
Protein Disulfide IsomeraseCatalyzes Disulfide Interchange
Protein Disulfide IsomeraseCatalyzes Disulfide Interchange
Protein Disulfide IsomeraseCatalyzes Disulfide Interchange
Box 6-4: Protein Structure Prediction & Protein Design
Hypothetical proteinsPDBids 1WHZ and 2HH6
Protein Folding & Disease
Alzheimer’s Disease: Amyloid Plaques
Prion Rods