Dimerization of hepatitis E virus capsid protein E2s domain is essential for virus-host interaction.
Dimerization of hepatitis E virus capsid protein E2s domain is essential for virus-host interaction.
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DOI：
10.1371/journal.ppat.1000537
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发表时间：
2009-08
期刊：
影响因子：
6.7
通讯作者：
Xia N
中科院分区：
文献类型：
--
作者：
Li S;Tang X;Seetharaman J;Yang C;Gu Y;Zhang J;Du H;Shih JW;Hew CL;Sivaraman J;Xia N
戊型肝炎病毒（HEV）是一种无包膜的正链RNA病毒，以粪-口方式传播，并在人类中引起急性肝病。HEV衣壳由衣壳组成，所述衣壳由形成病毒壳的单一结构衣壳蛋白的同源二聚体组成。这些二聚体被认为从病毒表面突出并与宿主细胞相互作用以引发感染。到目前为止，没有结构信息可用于任何HEV蛋白。在这里，我们首次报告的晶体结构的HEV衣壳蛋白结构域E2 s，一个突出的结构域，连同功能的研究，以说明该结构域形成一个紧密的同源二聚体，这种二聚化是必不可少的HEV-主机的相互作用。此外，我们还发现，中和抗体的HEV识别位点位于E2 s结构域。我们的研究将有助于开发疫苗，并随后开发针对HEV的特异性抑制剂。传染性病毒性肝炎是发展中国家和发达国家的主要疾病。戊型肝炎病毒（HEV）是人类和非人类灵长类动物严重肝脏炎症的主要原因之一，其特征在于黄疸、发热、肝肿大和腹痛。戊型肝炎病毒衣壳由单个亚单位组成，这些亚单位由形成病毒外壳的单个结构蛋白的同源二聚体组成。这些二聚体被认为从病毒表面突出并与宿主细胞相互作用以引发感染。到目前为止，没有结构信息可用于任何HEV蛋白。本文报道了HEV衣壳蛋白结构域E2 s（突出结构域）的晶体结构，沿着功能研究，说明E2 s的紧密同源二聚体状态，二聚化对HEV-宿主相互作用和疾病进展至关重要。我们还表明，中和抗体的HEV识别位点位于E2 s结构域。目前的研究结果将有助于HEV疫苗和新型抑制剂的开发。
Hepatitis E virus (HEV), a non-enveloped, positive-stranded RNA virus, is transmitted in a faecal-oral manner, and causes acute liver diseases in humans. The HEV capsid is made up of capsomeres consisting of homodimers of a single structural capsid protein forming the virus shell. These dimers are believed to protrude from the viral surface and to interact with host cells to initiate infection. To date, no structural information is available for any of the HEV proteins. Here, we report for the first time the crystal structure of the HEV capsid protein domain E2s, a protruding domain, together with functional studies to illustrate that this domain forms a tight homodimer and that this dimerization is essential for HEV–host interactions. In addition, we also show that the neutralizing antibody recognition site of HEV is located on the E2s domain. Our study will aid in the development of vaccines and, subsequently, specific inhibitors for HEV. Infectious viral hepatitis is a major disease in both developing and developed countries. Hepatitis E virus (HEV) is one of the major causes of severe inflammation of the liver, which is characterized by jaundice, fever, liver enlargement, and abdominal pain in humans and non-human primates. The hepatitis E virus capsid is made up of individual subunits consisting of homodimers of a single structural protein forming the virus shell. These dimers are believed to protrude from the viral surface and to interact with host cells to initiate infection. To date, no structural information is available for any of the HEV proteins. This article reports the crystal structure of the HEV capsid protein domain E2s (protruding domain), along with functional studies, which illustrate the tight homodimeric state of E2s and that dimerization is essential for both HEV–host interactions and disease progression. We also show that the neutralizing antibody recognition site of HEV is located on the E2s domain. The present findings will aid the development of vaccines and novel inhibitors for HEV.
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影响因子：
14.9
作者：
Holm, L;Sander, C
通讯作者：
Sander, C
影响因子：
3.4
作者：
Schuck, P
通讯作者：
Schuck, P
影响因子：
56.9
作者：
Prasad, BVV;Hardy, ME;Estes, MK
通讯作者：
Estes, MK
DOI：
10.1038/8263
发表时间：
1999-05-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
Perrakis, A;Morris, R;Lamzin, VS
通讯作者：
Lamzin, VS
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL