气候变化领域集成服务门户(CCPortal): Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility

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DOI	10.1073/pnas.2100370118
	Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility
	Grass L.M.; Wollenhaupt J.; Barthel T.; Parfentev I.; Urlaub H.; Loll B.; Klauck E.; Antelmann H.; Wahl M.C.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:30
英文摘要	Many bacteria harbor RNA-dependent nucleoside-triphosphatases of the DEAH/RHA family, whose molecular mechanisms and cellular functions are poorly understood. Here, we show that the Escherichia coli DEAH/RHA protein, HrpA, is an ATP-dependent 3 to 5′ RNA helicase and that the RNA helicase activity of HrpA influences bacterial survival under antibiotics treatment. Limited proteolysis, crystal structure analysis, and functional assays showed that HrpA contains an N-terminal DEAH/RHA helicase cassette preceded by a unique N-terminal domain and followed by a large C-terminal region that modulates the helicase activity. Structures of an expanded HrpA helicase cassette in the apo and RNA-bound states in combination with cross-linking/mass spectrometry revealed ratchet-like domain movements upon RNA engagement, much more pronounced than hitherto observed in related eukaryotic DEAH/RHA enzymes. Structure-based functional analyses delineated transient interdomain contact sites that support substrate loading and unwinding, suggesting that similar conformational changes support RNA translocation. Consistently, modeling studies showed that analogous dynamic intramolecular contacts are not possible in the related but helicase-inactive RNA-dependent nucleoside-triphosphatase, HrpB. Our results indicate that HrpA may be an interesting target to interfere with bacterial tolerance toward certain antibiotics and suggest possible interfering strategies. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	RNA-dependent NTPase/RNA helicase \| co-/posttranscriptional gene regulation \| antibiotics resistance \| X-ray crystallography \| structural biology
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238857
作者单位	Laboratory of Structural Biochemistry, Institute of Chemistry and Biochemistry, Freie Universität Berlin, Berlin, D-14195, Germany; Macromolecular Crystallography, Helmholtz-Zentrum Berlin für Materialien und Energie, Berlin, D-12489, Germany; Bioanalytical Mass Spectrometry, Max-Planck-Institut für biophysikalische Chemie, Göttingen, D-37077, Germany; Bioanalytics, Institute of Clinical Chemistry, Universitätsmedizin Göttingen, Göttingen, D-37075, Germany; Microbiology, Institute of Biology, Freie Universität Berlin, Berlin, D-14195, Germany
推荐引用方式 GB/T 7714	Grass L.M.,Wollenhaupt J.,Barthel T.,et al. Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility[J],2021,118(30).
APA	Grass L.M..,Wollenhaupt J..,Barthel T..,Parfentev I..,Urlaub H..,...&Wahl M.C..(2021).Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA	Grass L.M.,et al."Large-scale ratcheting in a bacterial DEAH/RHA-type RNA helicase that modulates antibiotics susceptibility".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).