6B3O

Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion

6B3O の概要

• エントリーDOI: 10.2210/pdb6b3o/pdb
• EMDBエントリー: 7040
• 分子名称: Spike glycoprotein (1 entity in total)
• 機能のキーワード: coronavirus, membrane fusion, mhv, sars, mers, viral protein
• 由来する生物種: Murine coronavirus (MHV-A59)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 198597.28

構造登録者

Walls, A.C.,Tortorici, M.A.,Snijder, J.,Xiong, X.,Bosch, B.J.,Rey, F.A.,Veesler, D. (登録日: 2017-09-22, 公開日: 2017-10-04, 最終更新日: 2024-11-13)

主引用文献

Walls, A.C.,Tortorici, M.A.,Snijder, J.,Xiong, X.,Bosch, B.J.,Rey, F.A.,Veesler, D.
Tectonic conformational changes of a coronavirus spike glycoprotein promote membrane fusion.
Proc. Natl. Acad. Sci. U.S.A., 114:11157-11162, 2017

PubMed Abstract: The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. The coronavirus spike (S) glycoprotein initiates infection by promoting fusion of the viral and cellular membranes through conformational changes that remain largely uncharacterized. Here we report the cryoEM structure of a coronavirus S glycoprotein in the postfusion state, showing large-scale secondary, tertiary, and quaternary rearrangements compared with the prefusion trimer and rationalizing the free-energy landscape of this conformational machine. We also biochemically characterized the molecular events associated with refolding of the metastable prefusion S glycoprotein to the postfusion conformation using limited proteolysis, mass spectrometry, and single-particle EM. The observed similarity between postfusion coronavirus S and paramyxovirus F structures demonstrates that a conserved refolding trajectory mediates entry of these viruses and supports the evolutionary relatedness of their fusion subunits. Finally, our data provide a structural framework for understanding the mode of neutralization of antibodies targeting the fusion machinery and for engineering next-generation subunit vaccines or inhibitors against this medically important virus family.

PubMed: 29073020
DOI: 10.1073/pnas.1708727114

実験手法

ELECTRON MICROSCOPY (4.1 Å)