Giuseppe
Emeritus
Cap binding and immune evasion revealed by Lassa nucleoprotein structure (Nature, abstract, edited)
[Source: Nature, full text: <cite cite="http://www.nature.com/nature/journal/v468/n7325/full/nature09605.html#/abstract">Cap binding and immune evasion revealed by Lassa nucleoprotein structure : Nature : Nature Publishing Group</cite>. Abstract, edited.]
Cap binding and immune evasion revealed by Lassa nucleoprotein structure
Xiaoxuan Qi, Shuiyun Lan, Wenjian Wang, Lisa McLay Schelde, Haohao Dong, Gregor D. Wallat, Hinh Ly, Yuying Liang & Changjiang Dong
Journal name: Nature
Volume: 468, Pages: 779?783
Date published: (09 December 2010)
DOI: doi:10.1038/nature09605
Received 07 May 2010
Accepted 25 October 2010
Published online 17 November 2010
Lassa virus, the causative agent of Lassa fever, causes thousands of deaths annually and is a biological threat agent, for which there is no vaccine and limited therapy. The nucleoprotein (NP) of Lassa virus has essential roles in viral RNA synthesis and immune suppression, the molecular mechanisms of which are poorly understood. Here we report the crystal structure of Lassa virus NP at 1.80 ? resolution, which reveals amino (N)- and carboxy (C)-terminal domains with structures unlike any of the reported viral NPs. The N domain folds into a novel structure with a deep cavity for binding the m7GpppN cap structure that is required for viral RNA transcription, whereas the C domain contains 3′?5′ exoribonuclease activity involved in suppressing interferon induction. To our knowledge this is the first X-ray crystal structure solved for an arenaviral NP, which reveals its unexpected functions and indicates unique mechanisms in cap binding and immune evasion. These findings provide great potential for vaccine and drug development.
Subject terms:
* Virology
* Structural biology
* Immunology
* Biochemistry
Affiliations
1. Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK * Xiaoxuan Qi, * Haohao Dong, * Gregor D. Wallat & * Changjiang Dong
2. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael St, Atlanta, Georgia 30322, USA * Shuiyun Lan, * Lisa McLay Schelde, * Hinh Ly & * Yuying Liang
3. Laboratory of Department of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China * Wenjian Wang
Contributions
X.Q., S.L., W.W., L.M.S., H.D. and G.D.W. performed experiments. C.D., Y.L. and H.L. conceived the idea for the study, performed some of the assays, participated in the analysis and interpretation of the data, and wrote the manuscript. All authors contributed to the final version of the manuscript.
Competing financial interests
The authors declare no competing financial interests.
Corresponding authors
Correspondence to: * Changjiang Dong or * Yuying Liang or * Hinh Ly
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[Source: Nature, full text: <cite cite="http://www.nature.com/nature/journal/v468/n7325/full/nature09605.html#/abstract">Cap binding and immune evasion revealed by Lassa nucleoprotein structure : Nature : Nature Publishing Group</cite>. Abstract, edited.]
Cap binding and immune evasion revealed by Lassa nucleoprotein structure
Xiaoxuan Qi, Shuiyun Lan, Wenjian Wang, Lisa McLay Schelde, Haohao Dong, Gregor D. Wallat, Hinh Ly, Yuying Liang & Changjiang Dong
Journal name: Nature
Volume: 468, Pages: 779?783
Date published: (09 December 2010)
DOI: doi:10.1038/nature09605
Received 07 May 2010
Accepted 25 October 2010
Published online 17 November 2010
Lassa virus, the causative agent of Lassa fever, causes thousands of deaths annually and is a biological threat agent, for which there is no vaccine and limited therapy. The nucleoprotein (NP) of Lassa virus has essential roles in viral RNA synthesis and immune suppression, the molecular mechanisms of which are poorly understood. Here we report the crystal structure of Lassa virus NP at 1.80 ? resolution, which reveals amino (N)- and carboxy (C)-terminal domains with structures unlike any of the reported viral NPs. The N domain folds into a novel structure with a deep cavity for binding the m7GpppN cap structure that is required for viral RNA transcription, whereas the C domain contains 3′?5′ exoribonuclease activity involved in suppressing interferon induction. To our knowledge this is the first X-ray crystal structure solved for an arenaviral NP, which reveals its unexpected functions and indicates unique mechanisms in cap binding and immune evasion. These findings provide great potential for vaccine and drug development.
Subject terms:
* Virology
* Structural biology
* Immunology
* Biochemistry
Affiliations
1. Biomedical Sciences Research Complex, School of Chemistry, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK * Xiaoxuan Qi, * Haohao Dong, * Gregor D. Wallat & * Changjiang Dong
2. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, 615 Michael St, Atlanta, Georgia 30322, USA * Shuiyun Lan, * Lisa McLay Schelde, * Hinh Ly & * Yuying Liang
3. Laboratory of Department of Surgery, The First Affiliated Hospital, Sun Yat-Sen University, 58 Zhongshan Road II, Guangzhou, Guangdong 510080, China * Wenjian Wang
Contributions
X.Q., S.L., W.W., L.M.S., H.D. and G.D.W. performed experiments. C.D., Y.L. and H.L. conceived the idea for the study, performed some of the assays, participated in the analysis and interpretation of the data, and wrote the manuscript. All authors contributed to the final version of the manuscript.
Competing financial interests
The authors declare no competing financial interests.
Corresponding authors
Correspondence to: * Changjiang Dong or * Yuying Liang or * Hinh Ly
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