An information theoretic framework reveals a tunable allosteric network in group II chaperonins

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• ATP-dependent allosteric regulation of group II chaperonins is poorly understood due to their complex structure.
• High sequence conservation in chaperonins complicates the identification of allosteric regulatory networks.

Purpose of the Study:

• To develop and apply an information-theoretic strategy to elucidate allosteric mechanisms in group II chaperonins.
• To identify the specific residues and networks involved in communication and cooperativity.

Main Methods:

• Application of an information-theoretic strategy robust to residue conservation.
• Analysis of residue covariation to map allosteric networks within chaperonin rings.

Main Results:

• Identification of a contiguous network of covarying residues connecting nucleotide-binding sites.
• Discovery of an interfacial residue that regulates positive cooperativity by communicating nucleotide occupancy.
• Demonstration that single mutations at this position can tune chaperonin allostery.

Conclusions:

• The study proposes a model where reduced chaperonin cooperativity, compared to maximal attainable levels, enhances protein folding robustness under diverse metabolic conditions.
• Naturally occurring variants with higher cooperativity are less common, supporting the proposed role of tunable cooperativity.