The nanoscale organization of the Nipah virus fusion protein informs new membrane fusion mechanisms.

IF 6.4 1区 生物学 Q1 BIOLOGY
eLife Pub Date : 2025-01-02 DOI:10.7554/eLife.97017
Qian Wang, Jinxin Liu, Yuhang Luo, Vicky Kliemke, Giuliana Leonarda Matta, Jingjing Wang, Qian Liu
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引用次数: 0

Abstract

Paramyxovirus membrane fusion requires an attachment protein for receptor binding and a fusion protein for membrane fusion triggering. Nipah virus (NiV) attachment protein (G) binds to ephrinB2 or -B3 receptors, and fusion protein (F) mediates membrane fusion. NiV-F is a class I fusion protein and is activated by endosomal cleavage. The crystal structure of a soluble GCN4-decorated NiV-F shows a hexamer-of-trimer assembly. Here, we used single-molecule localization microscopy to quantify the NiV-F distribution and organization on cell and virus-like particle membranes at a nanometer precision. We found that NiV-F on biological membranes forms distinctive clusters that are independent of endosomal cleavage or expression levels. The sequestration of NiV-F into dense clusters favors membrane fusion triggering. The nano-distribution and organization of NiV-F are susceptible to mutations at the hexamer-of-trimer interface, and the putative oligomerization motif on the transmembrane domain. We also show that NiV-F nanoclusters are maintained by NiV-F-AP-2 interactions and the clathrin coat assembly. We propose that the organization of NiV-F into nanoclusters facilitates membrane fusion triggering by a mixed population of NiV-F molecules with varied degrees of cleavage and opportunities for interacting with the NiV-G/receptor complex. These observations provide insights into the in situ organization and activation mechanisms of the NiV fusion machinery.

尼帕病毒融合蛋白的纳米级组织为新的膜融合机制提供了信息。
副粘病毒膜融合需要一个附着蛋白来结合受体,需要一个融合蛋白来触发膜融合。尼帕病毒(NiV)附着蛋白(G)与ephrinB2或-B3受体结合,融合蛋白(F)介导膜融合。NiV-F是一类融合蛋白,可通过内体切割激活。可溶性gcn4修饰NiV-F的晶体结构为六聚体的三聚体组装。在这里,我们使用单分子定位显微镜以纳米精度量化NiV-F在细胞和病毒样颗粒膜上的分布和组织。我们发现NiV-F在生物膜上形成独特的簇,不受内体切割或表达水平的影响。NiV-F被隔离成密集的簇有利于触发膜融合。NiV-F的纳米分布和组织容易受到六聚体-三聚体界面和跨膜域推定的寡聚基序突变的影响。我们还发现NiV-F纳米团簇是通过NiV-F- ap -2相互作用和网格蛋白包被组装来维持的。我们认为,NiV-F的纳米团簇结构促进了由不同程度切割的NiV-F分子混合群体引发的膜融合,并有机会与NiV-G/受体复合物相互作用。这些观察结果为NiV融合机制的原位组织和激活机制提供了见解。
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来源期刊
eLife
eLife BIOLOGY-
CiteScore
12.90
自引率
3.90%
发文量
3122
审稿时长
17 weeks
期刊介绍: eLife is a distinguished, not-for-profit, peer-reviewed open access scientific journal that specializes in the fields of biomedical and life sciences. eLife is known for its selective publication process, which includes a variety of article types such as: Research Articles: Detailed reports of original research findings. Short Reports: Concise presentations of significant findings that do not warrant a full-length research article. Tools and Resources: Descriptions of new tools, technologies, or resources that facilitate scientific research. Research Advances: Brief reports on significant scientific advancements that have immediate implications for the field. Scientific Correspondence: Short communications that comment on or provide additional information related to published articles. Review Articles: Comprehensive overviews of a specific topic or field within the life sciences.
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