PubMed Journals: Nucleic Acids Res

  Source:		PMID: 31131400

    		Nucleic Acids Res. 2019 Jul 9;47(12):6538-6550.
     		doi: 10.1093/nar/gkz409.

			Delicate structural coordination of the
			Severe Acute Respiratory Syndrome coronavirus
			Nsp13 upon ATP hydrolysis.

			Jia Z(1), Yan L(1), Ren Z(2), Wu L(3), Wang
			J(4), Guo J(5), Zheng L(1), Ming Z(6), Zhang
			L(1), Lou Z(1), Rao Z(1)(2)(3).

			Author Information
			(1) Laboratory of Structural Biology, School
			of Medicine, Tsinghua University, Beijing
			100084, China.
			(2) State Key Laboratory of Medicinal Chemical
			Biology, College of Life Science, Nankai
			University, Tianjin 300353, China.
			(3) Shanghai Institute for Advanced Immunochemical
			Studies and iHuman Institute, ShanghaiTech
			University, Shanghai 201210, China.
			(4) State Key Laboratory of Biotherapy,
			West China Hospital, Sichuan University,
			Chengdu 610041, China.
			(5) Protein Chemistry Facility, Center for
			Biomedical Analysis of Tsinghua University,
			Beijing 100084, China.
			(6) State Key Laboratory of Conservation
			and Utilization of Subtropical Agro-Bioresources,
			College of Life Science and Technology,
			Guangxi University, Nanning, China.

			To date, an effective therapeutic treatment
			that confers strong attenuation toward coronaviruses
			(CoVs) remains elusive. Of all the potential
			drug targets, the helicase of CoVs is considered
			to be one of the most important. Here, we
			first present the structure of the full-length
			Nsp13 helicase of SARS-CoV (SARS-Nsp13) and
			investigate the structural coordination
			of its five domains and how these contribute
			to its translocation and unwinding activity.
			A translocation model is proposed for the
			Upf1-like helicase members according to
			three different structural conditions in
			solution characterized through H/D exchange
			assay, including substrate state (SARS-Nsp13-dsDNA
			bound with AMPPNP), transition state (bound with ADP-AlF4-)
			and product state (bound with ADP). We observed
			that the β19-β20 loop on the 1A domain is
			involved in unwinding process directly.
			Furthermore, we have shown that the RNA
			dependent RNA polymerase (RdRp), SARS-Nsp12,
			can enhance the helicase activity of SARS-Nsp13
			through interacting with it directly. The interacting
			regions were identified and can be considered
			common across CoVs, which provides new insights
			into the Replication and Transcription Complex
			(RTC) of CoVs.

			© The Author(s) 2019. Published by Oxford
			University Press on behalf of Nucleic Acids

			DOI: 10.1093/nar/gkz409 PMCID: PMC6614802
			PMID: 31131400

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