Structures and distributions of SARS-CoV-2 spike proteins on intact virions.
Zunlong KeJoaquin OtónKun QuMirko CorteseVojtech ZilaLesley McKeaneTakanori NakaneJasenko ZivanovChristopher John NeufeldtBerati CerikanJohn M LuJulia PeukesXiaoli XiongHans-Georg KräusslichSjors H W ScheresRalf F W BartenschlagerJohn A G BriggsPublished in: Nature (2020)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude1. Heavily glycosylated S trimers bind to the angiotensin-converting enzyme 2 receptor and mediate entry of virions into target cells2-6. S exhibits extensive conformational flexibility: it modulates exposure of its receptor-binding site and subsequently undergoes complete structural rearrangement to drive fusion of viral and cellular membranes2,7,8. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy2,7,9-12, but the structure and distribution of S on the virion surface remain unknown. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions and determine the high-resolution structure, conformational flexibility and distribution of S trimers in situ on the virion surface. These results reveal the conformations of S on the virion, and provide a basis from which to understand interactions between S and neutralizing antibodies during infection or vaccination.
Keyphrases
- electron microscopy
- sars cov
- respiratory syndrome coronavirus
- high resolution
- angiotensin converting enzyme
- molecular dynamics
- angiotensin ii
- molecular dynamics simulations
- single molecule
- induced apoptosis
- binding protein
- cell cycle arrest
- deep learning
- genome wide
- endoplasmic reticulum stress
- cell death
- gene expression
- zika virus
- signaling pathway
- liquid chromatography
- monte carlo