Large-Scale Conformational Transitions and Dimerization Are Encoded in the Amino-Acid Sequences of Hsp70 Chaperones.

• Main Authors: Duccio Malinverni, Simone Marsili, Alessandro Barducci, Paolo De Los Rios
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2015-06-01
• Series: PLoS Computational Biology
• Online Access: http://europepmc.org/articles/PMC4457872?pdf=render

Hsp70s are a class of ubiquitous and highly conserved molecular chaperones playing a central role in the regulation of proteostasis in the cell. Hsp70s assist a myriad of cellular processes by binding unfolded or misfolded substrates during a complex biochemical cycle involving large-scale structural rearrangements. Here we show that an analysis of coevolution at the residue level fully captures the characteristic large-scale conformational transitions of this protein family, and predicts an evolutionary conserved-and thus functional-homo-dimeric arrangement. Furthermore, we highlight that the features encoding the Hsp70 dimer are more conserved in bacterial than in eukaryotic sequences, suggesting that the known Hsp70/Hsp110 hetero-dimer is a eukaryotic specialization built on a pre-existing template.