title: Information encoded in non-native states drives substrate-chaperone pairing.
abstract: Many proteins refold in vitro through kinetic folding intermediates that are believed to be by-products of native-state centric evolution. These intermediates are postulated to play only minor roles, if any, in vivo because they lack any information related to translation-associated vectorial folding. We demonstrate that refolding intermediate of a test protein, generated in vitro, is able to find its cognate chaperone, from the whole complement of Escherichia coli soluble chaperones. Cognate chaperone-binding uniquely alters the conformation of non-native substrate. Importantly, precise chaperone targeting of substrates are maintained as long as physiological molar ratios of chaperones remain unaltered. Using a library of different chaperone substrates, we demonstrate that kinetically trapped refolding intermediates contain sufficient structural features for precise targeting to cognate chaperones. We posit that evolution favors sequences that, in addition to coding for a functional native state, encode folding intermediates with higher affinity for cognate chaperones than noncognate ones.
authors: Proteomics and Structural Biology Unit, CSIR-Institute of Genomics and Integrative Biology, Mall Road, Delhi 110007, India. koyeli.mapa@igib.in
authors: Koyeli
authors: K
authors: Mapa
authors: Satyam
authors: S
authors: Tiwari
authors: Vignesh
authors: V
authors: Kumar
authors: Gopal Gunanathan
authors: GG
authors: Jayaraj
authors: Souvik
authors: S
authors: Maiti
mesh_terms: D019943:Amino Acid Substitution; D001426:Bacterial Proteins / Q000737:chemistry* / Q000302:isolation & purification; D002846:Chromatography, Affinity; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry* / Q000302:isolation & purification; D006360:Heat-Shock Proteins / Q000737:chemistry; D058619:Maltose-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011487:Protein Conformation; D025941:Protein Interaction Mapping; D058849:Protein Refolding; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; C028715:GroE protein, E coli; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D058619:Maltose-Binding Proteins; C057842:SecB protein, Bacteria; C063842:dnaK protein, E coli