Article abstract
Nature Structural & Molecular Biology 15, 1255 - 1262 (2008)
Published online: 16 November 2008 | doi:10.1038/nsmb.1515
Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies
Alice Y Yam1,4, Yu Xia2,4, Hen-Tzu Jill Lin3, Alma Burlingame3, Mark Gerstein2 & Judith Frydman1
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 
-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.
- Department of Biology and BioX Program, E200A James Clark Center, 318 Campus Drive, Stanford University, Stanford, California 94043, USA.
- Department of Molecular Biophysics & Biochemistry, PO Box 208114, Yale University, New Haven, Connecticut 06520, USA.
- Department of Pharmaceutical Chemistry, 600 16th Street, MC 2240, Genentech Hall, Suite N472A, University of California at San Francisco, San Francisco, California 94143, USA.
- Present addresses: Novartis Vaccines and Diagnostics, Inc., 4560 Horton Street, M/S 4.3, Emeryville, California 94608, USA (A.Y.Y.); Department of Chemistry, 44 Cummington Street, Boston University, Boston, Massachusetts 02215, USA (Y.X.).
Correspondence to: Judith Frydman1 e-mail: jfrydman@stanford.edu
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