Factors underlying asymmetric pore dynamics of disaggregase and microtubule-severing AAA+ machines.

ABSTRACT: Disaggregation and microtubule-severing nanomachines from the AAA+ (ATPases associated with various cellular activities) superfamily assemble into ring-shaped hexamers that enable protein remodeling by coupling large-scale conformational changes with application of mechanical forces within a central pore by loops protruding within the pore. We probed the asymmetric pore motions and intraring interactions that support them by performing extensive molecular dynamics simulations of single-ring severing proteins and the double-ring disaggregase ClpB. Simulations reveal that dynamic stability of hexameric pores of severing proteins and of the nucleotide-binding domain 1 (NBD1) ring of ClpB, which belong to the same clade, involves a network of salt bridges that connect conserved motifs of centr

SUBMITTER: Damre M 

PROVIDER: S-EPMC8391056 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature