title: Large-Scale Conformational Transitions and Dimerization Are Encoded in the Amino-Acid Sequences of Hsp70 Chaperones.
abstract: 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.
authors.affiliation: Laboratoire de Biophysique Statistique, École Polytechnique Fédérale de Lausanne, Faculté de Sciences de Base, Lausanne, Switzerland.
authors.forename: Duccio
authors.initials: D
authors.lastname: Malinverni
authors.affiliation: Structural Computational Biology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Simone
authors.initials: S
authors.lastname: Marsili
authors.affiliation: Laboratoire de Biophysique Statistique, École Polytechnique Fédérale de Lausanne, Faculté de Sciences de Base, Lausanne, Switzerland.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barducci
authors.affiliation: Laboratoire de Biophysique Statistique, École Polytechnique Fédérale de Lausanne, Faculté de Sciences de Base, Lausanne, Switzerland.
authors.forename: Paolo
authors.initials: P
authors.lastname: De Los Rios
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D019281:Dimerization; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D016415:Sequence Alignment
chemical_list: D005656:Fungal Proteins; D018840:HSP70 Heat-Shock Proteins