Chaperone client proteins evolve slower than non-client proteins

Area of Science:

• Molecular biology
• Evolutionary biology
• Protein biochemistry

Background:

• Molecular chaperones are essential for protein folding and function.
• Previous research suggested chaperones relax sequence constraints on client proteins, potentially allowing deleterious mutations.

Purpose of the Study:

• To investigate the evolutionary rates of chaperone client versus non-client proteins.
• To determine if chaperone assistance impacts protein evolution in natural conditions.

Main Methods:

• Comparative analysis of evolutionary rates.
• Examination of five model organisms (prokaryotic and eukaryotic).
• Assessment of folding rates and aggregation propensity.

Main Results:

• Chaperone client proteins exhibit significantly slower evolutionary rates across all studied organisms.
• Client proteins demonstrate slower folding rates and reduced aggregation propensity.
• These findings suggest chaperones mitigate the negative effects of mutations on protein folding.

Conclusions:

• Chaperones play a crucial role in maintaining protein homeostasis by counteracting deleterious mutations.
• The slower evolution of client proteins indicates a selective pressure against accumulating mutations that compromise protein structure/function.
• Organisms benefit from chaperone-assisted folding, preventing the fixation of potentially harmful mutations in natural populations.