Understanding the effect of secondary structures and aggregation on human protein folding class evolution

Area of Science:

• Evolutionary biology
• Structural biology
• Biophysics

Background:

• Protein designability correlates with contact density and buried residues, significantly impacting evolutionary rates.
• Previous studies established links between protein structure and evolution across various model organisms.

Purpose of the Study:

• To investigate factors influencing protein evolutionary rates in Homo sapiens.
• To examine the impact of secondary structure composition and solvent accessibility on human protein evolution.

Main Methods:

• Analysis of all-alpha and all-beta protein folding classes in Homo sapiens.
• Exploration of secondary structure composition (sheet and helix fractions) and solvent accessibility.
• Application of linear regression models to identify key predictive factors.

Main Results:

• Sheet fraction positively correlates with protein evolutionary rates, while helix fraction shows a negative correlation.
• Buried sheet fraction and relative aggregation propensity were identified as significant factors.
• Buried sheet fraction alone explains 9.9% of the variability in human protein evolution rates.

Conclusions:

• Secondary structure composition, particularly the fraction of buried sheet residues, is a key determinant of human protein evolutionary rates.
• The interplay between secondary structure and solvent accessibility provides insights into evolutionary dynamics.
• These findings contribute to understanding the molecular basis of protein evolution in humans.