Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases
Abstract
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.
- Authors:
-
- 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
- Publication Date:
- Research Org.:
- Univ. of Wisconsin, Madison, WI (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC); National Inst. of Health (NIH) (United States); Michigan Economic Development Corporation (United States); Michigan Technology Tri-Corridor (United States)
- OSTI Identifier:
- 1182325
- Grant/Contract Number:
- AC02-06CH11357; GM098885; GM07215; S10RR027000; P41GM103399; 085P1000817
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 112; Journal Issue: 14; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- ENGLISH
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES; helicase; RecQ; mechanism; aromatic-rich loop; DNA bending
Citation Formats
Manthei, Kelly A., Hill, Morgan C., Burke, Jordan E., Butcher, Samuel E., and Keck, James L. Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases. United States: N. p., 2015.
Web. doi:10.1073/pnas.1416746112.
Manthei, Kelly A., Hill, Morgan C., Burke, Jordan E., Butcher, Samuel E., & Keck, James L. Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases. United States. https://doi.org/10.1073/pnas.1416746112
Manthei, Kelly A., Hill, Morgan C., Burke, Jordan E., Butcher, Samuel E., and Keck, James L. Mon .
"Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases". United States. https://doi.org/10.1073/pnas.1416746112. https://www.osti.gov/servlets/purl/1182325.
@article{osti_1182325,
title = {Structural mechanisms of DNA binding and unwinding in bacterial RecQ helicases},
author = {Manthei, Kelly A. and Hill, Morgan C. and Burke, Jordan E. and Butcher, Samuel E. and Keck, James L.},
abstractNote = {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.},
doi = {10.1073/pnas.1416746112},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 14,
volume = 112,
place = {United States},
year = {Mon Mar 23 00:00:00 EDT 2015},
month = {Mon Mar 23 00:00:00 EDT 2015}
}
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