Dataset Information

Cryo electron microscopy of SARS-CoV-2 stabilized spike in prefusion state

ABSTRACT:

SUBMITTER: Jose Maria Carazo

PROVIDER: EMPIAR-10514 | biostudies-other |

REPOSITORIES: biostudies-other

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Publications

Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures.

Melero Roberto R Sorzano Carlos Oscar S COS Foster Brent B Vilas José-Luis JL Martínez Marta M Marabini Roberto R Ramírez-Aportela Erney E Sanchez-Garcia Ruben R Herreros David D Del Caño Laura L Losana Patricia P Fonseca-Reyna Yunior C YC Conesa Pablo P Wrapp Daniel D Chacon Pablo P McLellan Jason S JS Tagare Hemant D HD Carazo Jose-Maria JM

IUCrJ 20200929 Pt 6

Using a new consensus-based image-processing approach together with principal component analysis, the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state have been analysed. These studies revealed concerted motions involving the receptor-binding domain (RBD), N-terminal domain, and subdomains 1 and 2 around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. It is shown that in this data set there are not well defined, ...[more]

PMID: 33063791

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Project description:Porcine epidemic diarrhea virus (PEDV) is an alphacoronavirus that has a significant agricultural and economic impact due to the high mortality rate associated with infection of neonatal piglets. Like other coronaviruses, PEDV makes use of a large, trimeric spike (S) glycoprotein to mediate membrane fusion and gain entry into host cells. Despite the importance of the spike protein in viral entry and host immune responses, high-resolution structural information concerning this large macromolecular machine has been difficult to obtain. Here, we report the cryo-electron microscopy structure of the PEDV S protein in the prefusion conformation at a resolution of 3.1 Å. Our studies revealed that the sialic acid-binding domain at the N terminus of the S1 subunit has an orientation that is substantially different from that observed in the previously determined spike structure from human alphacoronavirus NL63. We also observed dissociated S1 subunit trimers wherein the putative receptor-binding domains exist in a conformation differing from that observed in the intact spike proteins, suggesting that the PEDV receptor-binding domain undergoes conformational rearrangements akin to those that have been described in the related betacoronaviruses. Collectively, these data provide new insights into the biological processes that mediate alphacoronavirus attachment, receptor engagement, and fusion triggering while also identifying a source of conformational heterogeneity that could be manipulated to improve PEDV vaccine antigens.IMPORTANCE Coronavirus spike proteins are large, densely glycosylated macromolecular machines that mediate receptor binding and membrane fusion to facilitate entry into host cells. This report describes the atomic-resolution structure of the spike protein from porcine epidemic diarrhea virus, a pathogenic alphacoronavirus that causes severe agricultural damage. The structure reveals a novel position for the sialic acid-binding attachment domain in the intact spike. We also observed shed fusion-suppressive capping subunits that displayed the putative receptor-binding domain in an accessible conformation. These observations provide a basis for understanding the molecular mechanisms that drive the earliest stages of alphacoronavirus infection and will inform future efforts to rationally design vaccines.

Dataset Information

Cryo electron microscopy of SARS-CoV-2 stabilized spike in prefusion state

Publications

Continuous flexibility analysis of SARS-CoV-2 spike prefusion structures.

Similar Datasets

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