Continuous millisecond conformational cycle of a DEAH box helicase reveals control of domain motions by atomic-scale transitions.

ABSTRACT: Helicases are motor enzymes found in every living organism and viruses, where they maintain the stability of the genome and control against false recombination. The DEAH-box helicase Prp43 plays a crucial role in pre-mRNA splicing in unicellular organisms by translocating single-stranded RNA. The molecular mechanisms and conformational transitions of helicases are not understood at the atomic level. We present a complete conformational cycle of RNA translocation by Prp43 in atomic detail based on molecular dynamics simulations. To enable the sampling of such complex transition on the millisecond timescale, we combined two enhanced sampling techniques, namely simulated tempering and adaptive sampling guided by crystallographic data. During RNA translocation, the center-of-mass motions of th

SUBMITTER: Becker RA 

PROVIDER: S-EPMC10082070 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature