Crystal structure of the Lassa virus nucleoprotein-RNA complex reveals a gating mechanism for RNA binding

被引:101
作者
Hastie, Kathryn M. [1 ]
Liu, Tong [3 ]
Li, Sheng [3 ]
King, Liam B. [1 ]
Nhi Ngo [1 ]
Zandonatti, Michelle A. [1 ]
Woods, Virgil L., Jr. [3 ]
de la Torre, Juan Carlos [1 ]
Saphire, Erica Ollmann [1 ,2 ]
机构
[1] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[3] Univ Calif San Diego, Dept Chem, La Jolla, CA 92093 USA
基金
美国国家卫生研究院;
关键词
structural biology; virology; MATRIX PROTEIN-Z; NUCLEOCAPSID PROTEIN; ANOMALOUS DIFFRACTION; FEVER; IDENTIFICATION; INHIBITION;
D O I
10.1073/pnas.1108515108
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Arenaviruses cause disease in industrialized and developing nations alike. Among them, the hemorrhagic fever virus Lassa is responsible for similar to 300,000-500,000 infections/y in Western Africa. The arenavirus nucleoprotein (NP) forms the protein scaffold of the genomic ribonucleoprotein complexes and is critical for transcription and replication of the viral genome. Here, we present crystal structures of the RNA-binding domain of Lassa virus NP in complex with ssRNA. This structure shows, in contrast to the predicted model, that RNA binds in a deep, basic crevice located entirely within the N-terminal domain. Furthermore, the NP-ssRNA structures presented here, combined with hydrogen-deuterium exchange/MS and functional studies, suggest a gating mechanism by which NP opens to accept RNA. Directed mutagenesis and functional studies provide a unique look into how the arenavirus NPs bind to and protect the viral genome and also suggest the likely assembly by which viral ribonucleoprotein complexes are organized.
引用
收藏
页码:19365 / 19370
页数:6
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