We apologize for Proteopedia being slow to respond. For the past two years, a new implementation of Proteopedia has been being built. Soon, it will replace this 18-year old system. All existing content will be moved to the new system at a date that will be announced here.

7po5

From Proteopedia

Jump to: navigation, search

Human coronavirus OC43 spike glycoprotein ectodomain in complex with the 47C9 antibody Fab fragment

Structural highlights

7po5 is a 9 chain structure with sequence from Homo sapiens and Human coronavirus OC43. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.9Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

SPIKE_CVHOC S1 attaches the virion to the cell membrane by interacting with sialic acid-containing cell receptors, initiating the infection. Attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099]

Publication Abstract from PubMed

Human coronavirus OC43 is a globally circulating common cold virus sustained by recurrent reinfections. How it persists in the population and defies existing herd immunity is unknown. Here we focus on viral glycoprotein S, the target for neutralizing antibodies, and provide an in-depth analysis of its antigenic structure. Neutralizing antibodies are directed to the sialoglycan-receptor binding site in S1(A) domain, but, remarkably, also to S1(B). The latter block infection yet do not prevent sialoglycan binding. While two distinct neutralizing S1(B) epitopes are readily accessible in the prefusion S trimer, other sites are occluded such that their accessibility must be subject to conformational changes in S during cell-entry. While non-neutralizing antibodies were broadly reactive against a collection of natural OC43 variants, neutralizing antibodies generally displayed restricted binding breadth. Our data provide a structure-based understanding of protective immunity and adaptive evolution for this endemic coronavirus which emerged in humans long before SARS-CoV-2.

Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes.,Wang C, Hesketh EL, Shamorkina TM, Li W, Franken PJ, Drabek D, van Haperen R, Townend S, van Kuppeveld FJM, Grosveld F, Ranson NA, Snijder J, de Groot RJ, Hurdiss DL, Bosch BJ Nat Commun. 2022 May 25;13(1):2921. doi: 10.1038/s41467-022-30658-0. PMID:35614127^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang C, Hesketh EL, Shamorkina TM, Li W, Franken PJ, Drabek D, van Haperen R, Townend S, van Kuppeveld FJM, Grosveld F, Ranson NA, Snijder J, de Groot RJ, Hurdiss DL, Bosch BJ. Antigenic structure of the human coronavirus OC43 spike reveals exposed and occluded neutralizing epitopes. Nat Commun. 2022 May 25;13(1):2921. doi: 10.1038/s41467-022-30658-0. PMID:35614127 doi:http://dx.doi.org/10.1038/s41467-022-30658-0