The group II chaperonin Mm‐Cpn binds and refolds human γD crystallin

Program in Structural and Computational Biology and Molecular Biophysics, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030
Protein Science (Impact Factor: 2.85). 01/2011; 20(1):30 - 41. DOI: 10.1002/pro.531


Chaperonins assist in the folding of nascent and misfolded proteins, though the mechanism of folding within the lumen of the chaperonin remains poorly understood. The archeal chaperonin from Methanococcus marapaludis, Mm-Cpn, shares the eightfold double barrel structure with other group II chaperonins, including the eukaryotic TRiC/CCT, required for actin and tubulin folding. However, Mm-Cpn is composed of a single species subunit, similar to group I chaperonin GroEL, rather than the eight subunit species needed for TRiC/CCT. Features of the β-sheet fold have been identified as sites of recognition by group II chaperonins. The crystallins, the major components of the vertebrate eye lens, are β-sheet proteins with two homologous Greek key domains. During refolding in vitro a partially folded intermediate is populated, and partitions between productive folding and off-pathway aggregation. We report here that in the presence of physiological concentrations of ATP, Mm-Cpn suppressed the aggregation of HγD-Crys by binding the partially folded intermediate. The complex was sufficiently stable to permit recovery by size exclusion chromatography. In the presence of ATP, Mm-Cpn promoted the refolding of the HγD-Crys intermediates to the native state. The ability of Mm-Cpn to bind and refold a human β-sheet protein suggests that Mm-Cpn may be useful as a simplified model for the substrate recognition mechanism of TRiC/CCT.

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Available from: Jonathan King, Oct 28, 2015
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    • "Among these are the ATP-driven group II chaperonins from eukaryotes and archaea that bear unique structural and functional characteristics (Cong et al., 2010; Ditzel et al., 1998; Zhang et al., 2010). The eukaryotic group II chaperonin TRiC/CCT is required to fold about 10% essential proteins newly synthesized from the ribosomes including tumor suppressors, cell cycle regulators, cytoskeletal proteins (Yam et al., 2008), and b sheet proteins (Knee et al., 2011). More intriguingly, a subset of its substrates, such as actin, can only be folded by TRiC but not other chaperon systems (Chen et al., 1994; Spiess et al., 2004), which implies its unique structural features and underlying mechanisms in protein folding. "
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