ATP-induced conformational changes in Hsp70: molecular dynamics and experimental validation of an in silico predicted conformation.

ABSTRACT: The 70 kDa heat shock proteins (Hsp70s) play important roles in preventing the misfolding of proteins and repairing damage under stress by coupling ATP binding and hydrolysis to protein substrate release and binding, respectively. ATP binding is believed to induce closing of the Hsp70 nucleotide binding domain (NBD) around the nucleotide. We report here a combined computational-experimental study of this open-closed transition. All-atom molecular dynamics simulations were performed for isolated open state NBDs with and without bound ATP. The nucleotide-free NBD samples a wide range of open configurations exhibiting flexible rearrangements of its four subdomains (IA-IIB). In contrast, the ATP-bound Hsp70 NBD closes to a range of configurations that is substantially more closed than the conf

SUBMITTER: Woo HJ 

PROVIDER: S-EPMC2787669 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature