title: Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies.
abstract: Folding within the crowded cellular milieu often requires assistance from molecular chaperones that prevent inappropriate interactions leading to aggregation and toxicity. The contribution of individual chaperones to folding the proteome remains elusive. Here we demonstrate that the eukaryotic chaperonin TRiC/CCT (TCP1-ring complex or chaperonin containing TCP1) has broad binding specificity in vitro, similar to the prokaryotic chaperonin GroEL. However, in vivo, TRiC substrate selection is not based solely on intrinsic determinants; instead, specificity is dictated by factors present during protein biogenesis. The identification of cellular substrates revealed that TRiC interacts with folding intermediates of a subset of structurally and functionally diverse polypeptides. Bioinformatics analysis revealed an enrichment in multidomain proteins and regions of beta-strand propensity that are predicted to be slow folding and aggregation prone. Thus, TRiC may have evolved to protect complex protein topologies within its central cavity during biosynthesis and folding.
authors.affiliation: Department of Biology and BioX Program, E200A James Clark Center, 318 Campus Drive, Stanford University, Stanford, California 94043, USA.
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Yam
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Hen-Tzu Jill
authors.initials: HT
authors.lastname: Lin
authors.forename: Alma
authors.initials: A
authors.lastname: Burlingame
authors.forename: Mark
authors.initials: M
authors.lastname: Gerstein
authors.forename: Judith
authors.initials: J
authors.lastname: Frydman
mesh_terms: D002478:Cells, Cultured; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry / Q000302:isolation & purification; D013379:Substrate Specificity
chemical_list: D011506:Proteins; C533304:TCP1 protein, human; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins