Conformational flexibility of fork-remodeling helicase Rad5 shown by full-ensemble hybrid methods

Gildenberg, Melissa S.; Washington, M. Todd

doi:10.1371/journal.pone.0223875

Conformational flexibility of fork-remodeling helicase Rad5 shown by full-ensemble hybrid methods

Journal Article · Fri Oct 18 00:00:00 EDT 2019 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0223875· OSTI ID:1581819

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Univ. of Iowa, Iowa City, IA (United States). College of Medicine

Several pathways exist to bypass DNA damage during replication. One such pathway is template switching. The Rad5 protein plays two important roles in template switching: it is an E3 ubiquitin ligase that catalyzes PCNA poly-ubiquitylation and it is a helicase that converts replication forks to chicken foot structures. To understand the structure, conformational flexibility, and mechanism of Rad5, we used a full-ensemble hybrid method combining Langevin dynamics simulations and small-angle X-ray scattering. From these studies, we generated the first experimentally validated, high-resolution structural model of Rad5. We found that Rad5 is more compact and less extended than is suggested by its large amount of predicted intrinsic disorder. Thus, Rad5 likely has a novel intra-molecular interaction that limits the range of conformational space it can sample. We provide evidence for a novel interaction between the HIRAN and the helicase domains of Rad5, and we discuss the biological and mechanistic implications of this.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Institute of Environmental Health Sciences (NIEHS); National Institute of General Medical Sciences (NIGMS); National Institutes of Health (NIH); USDOE Office of Science (SC)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1581819

Alternate ID(s):: OSTI ID: 1768958

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 10 Vol. 14; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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