Structural Analysis of Protein Folding by the Long-Chain Archaeal Chaperone FKBP26

In the cell, protein folding is mediated by folding catalysts and chaperones. The two functions are often linked, especially when the catalytic module forms part of a multidomain protein, as in Methanococcus jannaschii peptidyl-prolyl cis/ trans isomerase FKBP26. Here, we show that FKBP26 chaperone...

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Published inJournal of molecular biology Vol. 407; no. 3; pp. 450 - 464
Main Authors Martinez-Hackert, Erik, Hendrickson, Wayne A.
Format Journal Article
LanguageEnglish
Published England Elsevier Ltd 01.04.2011
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Summary:In the cell, protein folding is mediated by folding catalysts and chaperones. The two functions are often linked, especially when the catalytic module forms part of a multidomain protein, as in Methanococcus jannaschii peptidyl-prolyl cis/ trans isomerase FKBP26. Here, we show that FKBP26 chaperone activity requires both a 50-residue insertion in the catalytic FKBP domain, also called ‘Insert-in-Flap’ or IF domain, and an 80-residue C-terminal domain. We determined FKBP26 structures from four crystal forms and analyzed chaperone domains in light of their ability to mediate protein–protein interactions. FKBP26 is a crescent-shaped homodimer. We reason that folding proteins are bound inside the large crescent cleft, thus enabling their access to inward-facing peptidyl-prolyl cis/ trans isomerase catalytic sites and ipsilateral chaperone domain surfaces. As these chaperone surfaces participate extensively in crystal lattice contacts, we speculate that the observed lattice contacts reflect a proclivity for protein associations and represent substrate interactions by FKBP26 chaperone domains. Finally, we find that FKBP26 is an exceptionally flexible molecule, suggesting a mechanism for nonspecific substrate recognition.
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BNL-97570-2012-JA
DE-AC02-98CH10886
USDOE SC OFFICE OF SCIENCE (SC)
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2011.01.027