人类副病毒病原体 B19 的 VP1u N 端受体结合域的骨架核磁共振共振分配。

IF 0.8 4区 生物学 Q4 BIOPHYSICS
Maria Luiza Caldas Nogueira, Renuk Lakshmanan, Gwladys Rivière, Mario Mietzsch, Antonette Bennett, Robert McKenna, Joanna R. Long
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引用次数: 0

摘要

Parvovirus B19(B19V)是一种人类病原体,是婴儿和成人多种疾病的病原体。由于缺乏针对这种病毒的抗病毒药物,治疗方案十分有限。B19V 的小囊膜蛋白有一个独特的 N 末端,名为 VP1u,它对感染至关重要。VP1u 编码一个受体结合结构域(RBD)和一个磷脂酶 A2(PLA2)结构域,前者是宿主细胞进入病毒所必需的,后者则是细胞转运过程中内质体逃逸的关键。这两个结构域都是感染所不可或缺的,因此,RBD 位于病毒的外表面,是抑制 B19V 的药物靶点。迄今为止,还没有任何 Parvovirus VP1u 成分的实验结构信息。在此,我们报告了 B19V RBD 的骨架核磁共振共振分配,并证明它形成了稳定的结构。骨架化学位移与 AlphaFold 预测的结构非常吻合,验证了 RBD 包含三个由紧密转折连接的螺旋。这种 RBD 结构现在可用于进一步的核磁共振研究,包括全长 VP1u 的分配、蛋白质-蛋白质相互作用界面的确定以及针对 RBD 结构域的 B19 抗病毒药物的开发。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Backbone NMR resonance assignments for the VP1u N-terminal receptor-binding domain of the human parvovirus pathogen B19

Backbone NMR resonance assignments for the VP1u N-terminal receptor-binding domain of the human parvovirus pathogen B19

Backbone NMR resonance assignments for the VP1u N-terminal receptor-binding domain of the human parvovirus pathogen B19

Parvovirus B19 (B19V) is a human pathogen that is the causative agent of several diseases in infants and adults. Due to a lack of antivirals against this virus, treatment options are limited. The minor capsid protein of B19V has a unique N terminus, named VP1u, which is essential for infection. The VP1u encodes a receptor binding domain (RBD), necessary for host cell entry, and a phospholipase A2 (PLA2) domain, crucial for endosomal escape during cellular trafficking. Both domains are indispensable for infection, making the RBD a plausible drug target for inhibitors against B19V, as it is located on the exterior surface of the virus. To date, no experimental structural information has been available for the VP1u component for any Parvovirus. Here we report the backbone NMR resonance assignments for the RBD of B19V and demonstrate it forms a stable structure. The backbone chemical shifts are in good agreement with a structure predicted by AlphaFold, validating that the RBD contains three helices connected by tight turns. This RBD construct can now be used for further NMR studies, including assignment of full-length VP1u, determination of protein-protein interaction interfaces, and development of B19 antivirals specific to the RBD domain.

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来源期刊
Biomolecular NMR Assignments
Biomolecular NMR Assignments 生物-光谱学
CiteScore
1.70
自引率
11.10%
发文量
59
审稿时长
6-12 weeks
期刊介绍: Biomolecular NMR Assignments provides a forum for publishing sequence-specific resonance assignments for proteins and nucleic acids as Assignment Notes. Chemical shifts for NMR-active nuclei in macromolecules contain detailed information on molecular conformation and properties. Publication of resonance assignments in Biomolecular NMR Assignments ensures that these data are deposited into a public database at BioMagResBank (BMRB; http://www.bmrb.wisc.edu/), where they are available to other researchers. Coverage includes proteins and nucleic acids; Assignment Notes are processed for rapid online publication and are published in biannual online editions in June and December.
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