Proteins and Proteomics

  1. Protein Folding, Misfolding, and Denaturation
    1. The Protein Folding Process
      1. Thermodynamics of Folding
        1. Gibbs Free Energy
          1. Enthalpy and Entropy Contributions
            1. Marginal Stability of Proteins
            2. Kinetics of Folding
              1. Folding Rates and Mechanisms
                1. Two-State vs Multi-State Folding
                  1. Folding Intermediates
                  2. The Levinthal Paradox
                    1. Random Search Problem
                      1. Folding Funnel Concept
                      2. The Hydrophobic Effect as a Driving Force
                        1. Hydrophobic Collapse
                          1. Water Structure and Entropy
                          2. Energy Landscapes and Folding Funnels
                            1. Rugged vs Smooth Landscapes
                              1. Kinetic Traps
                                1. Folding Cooperativity
                                2. Molecular Chaperones
                                  1. Chaperonins
                                    1. GroEL/GroES System
                                      1. TRiC/CCT Complex
                                      2. Heat Shock Proteins
                                        1. Hsp70 Family
                                          1. Hsp90 Family
                                            1. Small Heat Shock Proteins
                                            2. Mechanisms of Chaperone Action
                                              1. Co-translational Folding
                                                1. Post-translational Assistance
                                                  1. Iterative Binding and Release
                                                2. Protein Disulfide Isomerases
                                                  1. Disulfide Bond Formation
                                                    1. Oxidative Folding Environment
                                                  2. Protein Denaturation
                                                    1. Definition: Loss of Native Structure
                                                      1. Denaturing Agents
                                                        1. Heat
                                                          1. Thermal Unfolding Curves
                                                            1. Melting Temperature
                                                            2. Extreme pH
                                                              1. Acid and Base Denaturation
                                                                1. Charge Effects
                                                                2. Organic Solvents
                                                                  1. Alcohol Effects
                                                                    1. Solvent Polarity
                                                                    2. Chaotropic Agents
                                                                      1. Urea
                                                                        1. Guanidinium Chloride
                                                                          1. Mechanism of Action
                                                                          2. Detergents
                                                                            1. SDS Denaturation
                                                                              1. Membrane Protein Solubilization
                                                                            2. Reversibility of Denaturation
                                                                              1. Anfinsen's Principle
                                                                                1. Conditions for Refolding
                                                                                2. Renaturation and Refolding
                                                                                  1. In Vitro Refolding
                                                                                    1. Refolding Yields
                                                                                      1. Aggregation Competition
                                                                                    2. Protein Misfolding and Aggregation
                                                                                      1. Mechanisms of Misfolding
                                                                                        1. Kinetic vs Thermodynamic Misfolding
                                                                                          1. Aggregation-Prone Sequences
                                                                                            1. Environmental Stress Factors
                                                                                            2. Types of Protein Aggregates
                                                                                              1. Amorphous Aggregates
                                                                                                1. Amyloid Fibrils
                                                                                                  1. Cross-Beta Structure
                                                                                                    1. Fibril Formation Mechanism
                                                                                                      1. Detection Methods
                                                                                                      2. Inclusion Bodies
                                                                                                        1. Prion-like Aggregates
                                                                                                        2. Cellular Mechanisms to Prevent Aggregation
                                                                                                          1. Proteostasis Networks
                                                                                                            1. Chaperone Systems
                                                                                                              1. Protein Quality Control
                                                                                                              2. Unfolded Protein Response
                                                                                                                1. Autophagy Pathways
                                                                                                                  1. Proteasomal Degradation

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                                                                                                              3. Protein Structure Determination Methods

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                                                                                                              5. Protein Function and Diversity