Structural determinants for protein unfolding and translocation by the Hsp104 protein disaggregase.

ABSTRACT: The ring-forming Hsp104 ATPase cooperates with Hsp70 and Hsp40 molecular chaperones to rescue stress-damaged proteins from both amorphous and amyloid-forming aggregates. The ability to do so relies upon pore loops present in the first ATP-binding domain (AAA-1; loop-1 and loop-2 ) and in the second ATP-binding domain (AAA-2; loop-3) of Hsp104, which face the protein translocating channel and couple ATP-driven changes in pore loop conformation to substrate translocation. A hallmark of loop-1 and loop-3 is an invariable and mutational sensitive aromatic amino acid (Tyr²⁵⁷ and Tyr⁶⁶²) involved in substrate binding. However, the role of conserved aliphatic residues (Lys²⁵⁶, Lys²⁵⁸, and Val⁶⁶³) flanking the pore loop tyrosines, and the func

SUBMITTER: Lee J 

PROVIDER: S-EPMC5741831 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature