Flavivirus NS1 Structures Reveal Surfaces for Associations with Membranes and the Immune System

被引：302

作者：

Akey, David L. ^{[1
]}

Brown, W. Clay ^{[1
]}

Dutta, Somnath ^{[1
]}

Konwerski, Jamie ^{[1
]}

Jose, Joyce ^{[2
]}

Jurkiw, Thomas J. ^{[1
]}

DelProposto, James ^{[1
]}

Ogata, Craig M. ^{[3
]}

Skiniotis, Georgios ^{[1
,4
]}

Kuhn, Richard J. ^{[2
,5
]}

Smith, Janet L. ^{[1
,4
]}

机构：

[1] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA

[2] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA

[3] Argonne Natl Lab, Adv Photon Source, GM CA APS, Argonne, IL 60439 USA

[4] Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA

[5] Purdue Univ, Bindley Biosci Ctr, W Lafayette, IN 47907 USA

来源：

SCIENCE | 2014年 / 343卷 / 6173期

关键词：

NONSTRUCTURAL PROTEIN NS1; WEST-NILE-VIRUS; RNA REPLICATION; MONOCLONAL-ANTIBODIES; COMPLEMENT ACTIVATION; COMMON EPITOPES; INFECTED-CELLS; PATHOGENESIS; BIOLOGY; BINDING;

D O I：

10.1126/science.1247749

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：

Flaviviruses, the human pathogens responsible for dengue fever, West Nile fever, tick-borne encephalitis, and yellow fever, are endemic in tropical and temperate parts of the world. The flavivirus nonstructural protein 1 (NS1) functions in genome replication as an intracellular dimer and in immune system evasion as a secreted hexamer. We report crystal structures for full-length, glycosylated NS1 from West Nile and dengue viruses. The NS1 hexamer in crystal structures is similar to a solution hexamer visualized by single-particle electron microscopy. Recombinant NS1 binds to lipid bilayers and remodels large liposomes into lipoprotein nanoparticles. The NS1 structures reveal distinct domains for membrane association of the dimer and interactions with the immune system and are a basis for elucidating the molecular mechanism of NS1 function.

引用

页码：881 / 885

页数：5

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