Crystal structure of C1pA, an Hsp100 chaperone and regulator of C1pAP protease

Abstract

Escherichia coli C1pA, an Hsp100/C1p chaperone and an integral component of the ATP-dependent C1pAP protease, participates in regulatory protein degradation and the dissolution and degradation of protein aggregates. The crystal structure of the C1pA subunit reveals an N-terminal domain with pseudo-twofold symmetry and two AAA+ modules (D1 and D2) each consisting of a large and a small sub-domain with ADP bound in the sub-domain junction. The N-terminal domain interacts with the D1 domain in a manner similar to adaptor-binding domains of other AAA+ proteins. D1 and D2 are connected head-to-tail consistent with a cooperative and vectorial translocation of protein substrates. In a planar hexamer model of C1pA, built by assembling C1pA D1 and D2 into homohexameric rings of known structures of AAA+ modules, the differences in D1-D1 and D2-D2 interfaces correlate with their respective contributions to hexamer stability and ATPase activity.