A mutant chaperonin with rearranged inter-ring electrostatic contacts and temperature-sensitive dissociation

B. Trevor Sewell, Robert B. Best, Shaoxia Chen, Alan M. Roseman, George W. Farr, Arthur L. Horwich, Helen R. Saibil

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The chaperonin GroEL assists protein folding through ATP-dependent, cooperative movements that alternately create folding chambers in its two rings. The substitution E461K at the interface between these two rings causes temperature-sensitive, defective protein folding in Escherichia coli. To understand the molecular defect, we have examined the mutant chaperonin by cryo-EM. The normal out-of-register alignment of contacts between subunits of opposing wild-type rings is changed in E461K to an in-register one. This is associated with loss of cooperativity in ATP binding and hydrolysis. Consistent with the loss of negative cooperativity between rings, the cochaperonin GroES binds simultaneously to both E461K rings. These GroES-bound structures were unstable at higher temperature, dissociating into complexes of single E461K rings associated with GroES. Lacking the allosteric signal from the opposite ring, these complexes cannot release their GroES and become trapped, dead-end states.
    Original languageEnglish
    Pages (from-to)1128-1133
    Number of pages5
    JournalNature Structural and Molecular Biology
    Volume11
    Issue number11
    DOIs
    Publication statusPublished - Nov 2004

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