Identification of key hinge residues important for nucleotide-dependent allostery in E. coli Hsp70/DnaK.

ABSTRACT: DnaK is a molecular chaperone that has important roles in protein folding. The hydrolysis of ATP is essential to this activity, and the effects of nucleotides on the structure and function of DnaK have been extensively studied. However, the key residues that govern the conformational motions that define the apo, ATP-bound, and ADP-bound states are not entirely clear. Here, we used molecular dynamics simulations, mutagenesis, and enzymatic assays to explore the molecular basis of this process. Simulations of DnaK's nucleotide-binding domain (NBD) in the apo, ATP-bound, and ADP/Pi-bound states suggested that each state has a distinct conformation, consistent with available biochemical and structural information. The simulations further suggested that large shearing motions between subdomains

SUBMITTER: Ung PM 

PROVIDER: S-EPMC3836694 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature