Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases

Manthei, Kelly A.; Hill, Morgan C.; Burke, Jordan E.; Butcher, Samuel E.; Keck, James L.

doi:10.1073/pnas.1416746112

Title: Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases

Journal Article · Mon Mar 23 00:00:00 EDT 2015 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1416746112· OSTI ID:1182325

Manthei, Kelly A. ^[1]; Hill, Morgan C. ^[1]; Burke, Jordan E. ^[2]; Butcher, Samuel E. ^[2]; Keck, James L. ^[1]

Univ. of Wisconsin, Madison, WI (United States). School of Medicine and Public Health. Dept. of Biomolecular Chemistry
Univ. of Wisconsin, Madison, WI (United States). Dept. of Biochemistry

RecQ helicases unwind remarkably diverse DNA structures as key components of many cellular processes. How RecQ enzymes accommodate different substrates in a unified mechanism that couples ATP hydrolysis to DNA unwinding is unknown. In this paper, the X-ray crystal structure of the Cronobacter sakazakii RecQ catalytic core domain bound to duplex DNA with a 3' single-stranded extension identifies two DNA-dependent conformational rearrangements: a winged-helix domain pivots ~90° to close onto duplex DNA, and a conserved aromatic-rich loop is remodeled to bind ssDNA. These changes coincide with a restructuring of the RecQ ATPase active site that positions catalytic residues for ATP hydrolysis. Complex formation also induces a tight bend in the DNA and melts a portion of the duplex. Finally, this bending, coupled with translocation, could provide RecQ with a mechanism for unwinding duplex and other DNA structures.

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Research Organization:: Univ. of Wisconsin, Madison, WI (United States)

Sponsoring Organization:: USDOE Office of Science (SC); National Inst. of Health (NIH) (United States); Michigan Economic Development Corporation (United States); Michigan Technology Tri-Corridor (United States)

Grant/Contract Number:: AC02-06CH11357; GM098885; GM07215; S10RR027000; P41GM103399; 085P1000817

OSTI ID:: 1182325

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Vol. 112, Issue 14; ISSN 0027-8424

Publisher:: National Academy of Sciences, Washington, DC (United States)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 49 works

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RecQ and Fe–S helicases have unique roles in DNA metabolism dictated by their unwinding directionality, substrate specificity, and protein interactions Estep, Katrina N.; Brosh, Robert M. Biochemical Society Transactions, Vol. 46, Issue 1 https://doi.org/10.1042/bst20170044	journal	December 2017
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Single-molecule visualization of RecQ helicase reveals DNA melting, nucleation, and assembly are required for processive DNA unwinding Rad, Behzad; Forget, Anthony L.; Baskin, Ronald J. Proceedings of the National Academy of Sciences, Vol. 112, Issue 50 https://doi.org/10.1073/pnas.1518028112	journal	November 2015
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Crystal structure of the Bloom's syndrome helicase indicates a role for the HRDC domain in conformational changes Newman, Joseph A.; Savitsky, Pavel; Allerston, Charles K. Nucleic Acids Research, Vol. 43, Issue 10 https://doi.org/10.1093/nar/gkv373	journal	April 2015
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Single molecule kinetics uncover roles for E. coli RecQ DNA helicase domains and interaction with SSB Bagchi, Debjani; Manosas, Maria; Zhang, Weiting Nucleic Acids Research, Vol. 46, Issue 16 https://doi.org/10.1093/nar/gky647	journal	July 2018
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The structural and functional characterization of human RecQ4 reveals insights into its helicase mechanism Kaiser, Sebastian; Sauer, Florian; Kisker, Caroline Nature Communications, Vol. 8, Issue 1 https://doi.org/10.1038/ncomms15907	journal	June 2017
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59 BASIC BIOLOGICAL SCIENCES
helicase
RecQ
mechanism
aromatic-rich loop
DNA bending

Title: Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases

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