Protein Aggregation:

Introduction
• Proteins are biochemical compounds consisting of
one or more polypeptides typically folded into a
globular or fibrous form, facilitating a biological
function.
• Protein aggregation is a common cause of protein
instability.
• Protein aggregates show reduced or no biological
activity and are toxic.
• They are associated with neurodegenerative
disorders such as Parkinson’s, Alzheimer’s etc.
 Protein Aggregation

Physical Chemical
No change in primary structure Formation of new covalent
bonds
 Mechanisms of Protein Aggregation

• Subsequent Monomer Addition (Oosawa et al 1962)

 Aggregation of G-actin to F-actin
 Resembles condensation reaction
 Aggregation occurs only above a critical concentration
Modification by Hofrichter et al (1974)
 Sickle cell hemoglobin gelation
 Distinguished between nucleation and polymerization
 Addition steps of nucleation are assumed thermodynamically
unfavorable till critical nucleus formation followed by
favorable polymerization
 Critical nucleus is the minimum sized oligomer capable of
initiating furthur growth.
 Introduced an expression for the rate of formation of critical
nucleus
 Drawbacks: Inability to predict the shape of early portion of
aggregation curve