Allosteric response is both conserved and variable across three CheY orthologs

Area of Science:

• Computational biology
• Structural biology
• Biophysics

Background:

• Allosteric signaling is crucial for protein function and regulation.
• Identifying residues that initiate allosteric signals remains a challenge.
• Bacterial chemotaxis protein Y (CheY) is a key signaling molecule.

Purpose of the Study:

• To develop and apply a computational method for identifying allosteric signal initiation sites.
• To compare allosteric response patterns across different CheY orthologs.
• To investigate the evolutionary conservation and variability of intraprotein communication.

Main Methods:

• Developed a computational approach based on stability and flexibility profile differences.
• Utilized a distance constraint model to analyze wild-type and perturbed protein structures.
• Applied the method to three bacterial CheY orthologs.

Main Results:

• Identified residues likely to initiate allosteric signals in CheY orthologs.
• Observed a combination of conserved and variable allosteric sites.
• Found that >50% of putative sites were specific to single orthologs.
• Highlighted four allosteric hotspots, including the critical β4/α4 loop.

Conclusions:

• Intraprotein communication descriptions are more variable than protein structure and function.
• Allosteric response patterns show evolutionary relationships but also significant divergence.
• The identified hotspots are crucial for relaying signals, such as phosphorylation in CheY.