The crystal structure of vaccinia virus protein E2 and perspectives on the prediction of novel viral protein folds.
The crystal structure of vaccinia virus protein E2 and perspectives on the prediction of novel viral protein folds.
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DOI：
10.1099/jgv.0.001716
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Graham SC
中科院分区：
文献类型：
--
作者：
Gao WND;Gao C;Deane JE;Carpentier DCJ;Smith GL;Graham SC
痘苗病毒（VACV，痘病毒科）（天花疫苗）的形态发生是一个复杂的过程，涉及多个不同的细胞膜，并产生多种不同形式的感染性病毒粒子。有包膜病毒粒子的有效释放（促进宿主内感染的全身性传播）需要VACV蛋白E2，但E2功能的分子基础仍不清楚，并且E2缺乏与任何明确表征的蛋白质家族的序列同源性。我们以 2.3 Å 分辨率解析了 VACV E2 的晶体结构，揭示了它包含两个具有新颖折叠的结构域：N 端环形结构域和 C 端球状（头）结构域。 C 端头结构域与细胞（假）激酶表现出较弱的结构同源性，但缺乏保守的表面残基或激酶特征，表明它不具有酶活性，并且具有可能与磷酸肌醇脂质头基相互作用的大表面碱性斑块。最近的深度学习方法彻底改变了我们仅根据一级序列预测蛋白质三维结构的能力。 VACV E2 是结构预测的“困难”病毒蛋白靶标的范例，由多个新结构域组成，并且缺乏痘病毒科以外的序列同源物。尽管如此，AlphaFold2 仍然成功地分别以高准确度和中等准确度预测了头域和环域的结构，从而可以准确推断多种结构特性。高度准确的病毒结构预测的出现标志着结构病毒学的一步变化，并预示着结构信息分子病毒学的新时代。
The morphogenesis of vaccinia virus (VACV, family Poxviridae), the smallpox vaccine, is a complex process involving multiple distinct cellular membranes and resulting in multiple different forms of infectious virion. Efficient release of enveloped virions, which promote systemic spread of infection within hosts, requires the VACV protein E2 but the molecular basis of E2 function remains unclear and E2 lacks sequence homology to any well-characterised family of proteins. We solved the crystal structure of VACV E2 to 2.3 Å resolution, revealing that it comprises two domains with novel folds: an N-terminal annular (ring) domain and a C-terminal globular (head) domain. The C-terminal head domain displays weak structural homology with cellular (pseudo)kinases but lacks conserved surface residues or kinase features, suggesting that it is not enzymatically active, and possesses a large surface basic patch that might interact with phosphoinositide lipid headgroups. Recent deep learning methods have revolutionised our ability to predict the three-dimensional structures of proteins from primary sequence alone. VACV E2 is an exemplar ‘difficult’ viral protein target for structure prediction, being comprised of multiple novel domains and lacking sequence homologues outside Poxviridae. AlphaFold2 nonetheless succeeds in predicting the structures of the head and ring domains with high and moderate accuracy, respectively, allowing accurate inference of multiple structural properties. The advent of highly accurate virus structure prediction marks a step-change in structural virology and beckons a new era of structurally-informed molecular virology.
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影响因子：
64.8
作者：
Jumper J;Evans R;Pritzel A;Green T;Figurnov M;Ronneberger O;Tunyasuvunakool K;Bates R;Žídek A;Potapenko A;Bridgland A;Meyer C;Kohl SAA;Ballard AJ;Cowie A;Romera-Paredes B;Nikolov S;Jain R;Adler J;Back T;Petersen S;Reiman D;Clancy E;Zielinski M;Steinegger M;Pacholska M;Berghammer T;Bodenstein S;Silver D;Vinyals O;Senior AW;Kavukcuoglu K;Kohli P;Hassabis D
通讯作者：
Hassabis D
影响因子：
14.9
作者：
KELMAN, Z;ODONNELL, M
通讯作者：
ODONNELL, M
影响因子：
5.6
作者：
LEE, B;RICHARDS, FM
通讯作者：
RICHARDS, FM
DOI：
10.2807/1560-7917.es.2021.26.32.2100745
发表时间：
2021-08
期刊：
Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin
影响因子：
--
作者：
Hobson G;Adamson J;Adler H;Firth R;Gould S;Houlihan C;Johnson C;Porter D;Rampling T;Ratcliffe L;Russell K;Shankar AG;Wingfield T
通讯作者：
Wingfield T
影响因子：
6.7
作者：
Graham SC;Bahar MW;Cooray S;Chen RA;Whalen DM;Abrescia NG;Alderton D;Owens RJ;Stuart DI;Smith GL;Grimes JM
通讯作者：
Grimes JM