title: Promiscuous substrate recognition in folding and assembly activities of the trigger factor chaperone.
abstract: Trigger factor (TF) is a molecular chaperone that binds to bacterial ribosomes where it contacts emerging nascent chains, but TF is also abundant free in the cytosol where its activity is less well characterized. In vitro studies show that TF promotes protein refolding. We find here that ribosome-free TF stably associates with and rescues from misfolding a large repertoire of full-length proteins. We identify over 170 members of this cytosolic Escherichia coli TF substrate proteome, including ribosomal protein S7. We analyzed the biochemical properties of a TF:S7 complex from Thermotoga maritima and determined its crystal structure. Thereby, we obtained an atomic-level picture of a promiscuous chaperone in complex with a physiological substrate protein. The structure of the complex reveals the molecular basis of substrate recognition by TF, indicates how TF could accelerate protein folding, and suggests a role for TF in the biogenesis of protein complexes.
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Martinez-Hackert
authors.forename: Wayne A
authors.initials: WA
authors.lastname: Hendrickson
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry*; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry; D019696:Peptidylprolyl Isomerase / Q000737:chemistry*; D017510:Protein Folding; D020543:Proteome / Q000032:analysis; D012269:Ribosomal Proteins / Q000378:metabolism; D020124:Thermotoga maritima / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D020543:Proteome; D012269:Ribosomal Proteins; C403324:trigger factor, E coli; D019696:Peptidylprolyl Isomerase