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

• Published in: Journal of molecular biology Vol. 407; no. 3; pp. 450 - 464
• Main Authors: Martinez-Hackert, Erik, Hendrickson, Wayne A.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.04.2011
• Subjects: 60 APPLIED LIFE SCIENCES; Archaeal Proteins - chemistry; Archaeal Proteins - metabolism; BASIC BIOLOGICAL SCIENCES; Binding Sites; Catalysis; CATALYSTS; CRYSTAL LATTICES; CRYSTAL STRUCTURE; FKBP; ISOMERASES; Methanococcus; Methanococcus - enzymology; Models, Molecular; Molecular Chaperones - chemistry; Molecular Chaperones - metabolism; Peptidylprolyl Isomerase - chemistry; Peptidylprolyl Isomerase - metabolism; PPIase; prolyl isomerase; Protein Folding; Protein Structure, Tertiary; PROTEINS; protein–protein interactions; SUBSTRATES; Surface Properties; protein–protein interactions; MAD; TF; CTD; FKBP; FKBP26; PPIase; crystal structure; prolyl isomerase; SeMet; IF
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2011.01.027

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.