Distinct dissociation rates of murine and human norovirus P-domain dimers suggest a role of dimer stability in virus-host interactions.
Distinct dissociation rates of murine and human norovirus P-domain dimers suggest a role of dimer stability in virus-host interactions.
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DOI：
10.1038/s42003-022-03497-4
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发表时间：
2022-06-09
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
诺如病毒衣壳是由90个主要衣壳蛋白VP1二聚体组成的二十面体颗粒。VP1蛋白的c端形成一个突出的(P)结构域，介导受体附着，并为中和抗体提供靶标。核磁共振和天然质谱可直接检测小鼠（MNV）溶液中的p结构域单体，但不能检测人诺如病毒（HuNoV）溶液中的p结构域单体。我们报道，糖鹅脱氧胆酸（GCDCA）的结合稳定了MNV-1 p -结构域二聚体（p -二聚体），并在抗体和受体结合的环内诱导了远程NMR化学位移扰动（csp），可能反映了相应的构象变化。对浓度依赖性甲基TROSY NMR谱中单体和二聚体交叉峰的整体线形分析得出MNV-1 p -二聚体的解离速率常数koff约为1 s−1。对于结构密切相关的HuNoV GII.4 Saga p -二聚体，离子交换色谱得到的值约为10−6 s−1，表明GCDCA作为MNV和HuNoV感染的辅助因子的作用存在本质差异。核磁共振和天然质谱分析表明，鼠和人诺如病毒的主要衣壳VP1蛋白表现出不同的行为，并受到糖鹅脱氧胆酸结合的不同调节。
Norovirus capsids are icosahedral particles composed of 90 dimers of the major capsid protein VP1. The C-terminus of the VP1 proteins forms a protruding (P)-domain, mediating receptor attachment, and providing a target for neutralizing antibodies. NMR and native mass spectrometry directly detect P-domain monomers in solution for murine (MNV) but not for human norovirus (HuNoV). We report that the binding of glycochenodeoxycholic acid (GCDCA) stabilizes MNV-1 P-domain dimers (P-dimers) and induces long-range NMR chemical shift perturbations (CSPs) within loops involved in antibody and receptor binding, likely reflecting corresponding conformational changes. Global line shape analysis of monomer and dimer cross-peaks in concentration-dependent methyl TROSY NMR spectra yields a dissociation rate constant koff of about 1 s−1 for MNV-1 P-dimers. For structurally closely related HuNoV GII.4 Saga P-dimers a value of about 10−6 s−1 is obtained from ion-exchange chromatography, suggesting essential differences in the role of GCDCA as a cofactor for MNV and HuNoV infection. NMR and native mass spectrometry reveal that the major capsid VP1 protein from murine and human norovirus exhibit distinct behaviors and are differentially regulated by the binding of glycochenodeoxycholic acid.
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影响因子：
--
作者：
Hwang, Seungmin;Alhatlani, Bader;Arias, Armando;Caddy, Sarah L;Christodoulou, Constantina;Cunha, Juliana Bragazza;Emmott, Ed;Gonzalez-Hernandez, Marta;Kolawole, Abimbola;Lu, Jia;Rippinger, Christine;Sorgeloos, Frederic;Thorne, Lucy;Vashist, Surender;Goodfellow, Ian;Wobus, Christiane E
通讯作者：
Wobus, Christiane E
DOI：
10.1016/j.pnmrs.2013.12.001
发表时间：
2014-04
影响因子：
6.1
作者：
Frueh, Dominique P.
通讯作者：
Frueh, Dominique P.
影响因子：
5
作者：
Perry, Jeffrey W.;Taube, Stefan;Wobus, Christiane E.
通讯作者：
Wobus, Christiane E.
影响因子：
3.2
作者：
Creutznacher, Robert;Schulze, Eric;Mallagaray, Alvaro
通讯作者：
Mallagaray, Alvaro
影响因子：
6.7
作者：
Graziano, Vincent R.;Walker, Forrest C.;Wilen, Craig B.
通讯作者：
Wilen, Craig B.