7.88J | Spring 2015 | Graduate

Protein Folding and Human Disease


1 Introduction to Class

  1. Introduction to Class; Objectives, Format, Schedule, Student Introductions
  2. Features of the Universe of known Protein Sequences and Structures
  3. The Anfinsen Experiments

2 Protein Conformation Review

  1. Fibrous Proteins
  2. Pauling-corey α-helix
  3. Helix / helix Packing in Globular Proteins; Helix / Helix Packing in Coiled Coils
  4. Amino Acid Sequence Control of Helicity; Helix Start and Stop Signals

Assignment 1 due
3 β-sheet Conformations

  1. β-sheet Conformations
  2. Sheet / Sheet Packing in Parallel β-sheets
  3. In Orthogonal β-sheets
  4. β-helices

Assignment 2 due
4 Critical Features of in Vitro Refolding Reactions

  1. Failure of Refolding and Off-pathway Aggregation
  2. Industrial Scale Refolding in the Biotechnology Industry

Assignment 3 due
5 Structure and Function of Double Barrel Chaperonins

  1. I. Prokaryotic GroE / L, Archael Mm-Cpn, and Eukaryotic TRiC
  2. Temperature Sensitive Folding Mutants

Assignment 4 due

Amyloid Fibers and Neurodegenerative Disease

In-Class Guest Lecturer: Prof. Peter Lansbury, Harvard Medical School, “Synuclein as a Therapeutic Target for Parkinson’s Disease: Twenty Years and Counting.”

Assignment 5 due
7 Collagen Folding and Assembly

  1. Collagen Triple Helix
  2. Forces that Stabilize
  3. Collagen-based Birth Defects

Assignment 6 due
8 Protein Deposition Diseases: Light Chain Amyloidosis, Alzheimers, Parkinson’s, Huntington’s, ALS and Others

In-Class Guest Lecturer: Dr. Kelly Knee, Pfizer, Cambridge, “Sickle Cell Hemoglobin.”

Assignment 7 due
9 Prions and Functional Amyloids  
10 Membrane Proteins

  1. Domain-swapping, Loop-sheet Insertion, and Other Pathways for Protein Aggregation / Polymerization

11 Chaperones

  1. Ribosome Tunnel, Trigger Factor, HSP 40, HSP 70 and HSP 90 Chaperones
  2. ER Chaperones
  3. Proteasome and Degradation Pathways

12 Student Paper Presentations

  1. Introduction to Class; Objectives, Format, Schedule, Student Introductions
  2. ALS
  3. DNAK / Trigger Factor

13 Student Paper Presentations

  1. Light Chain Amyloidosis
  2. Parkinsons

14 Student Paper Presentations

  1. Alzheimers

Final Papers due

Course Info

As Taught In
Spring 2015
Learning Resource Types
Written Assignments