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http://conacyt.repositorioinstitucional.mx/jspui/handle/1000/7463| Relationship between monomer packing and receptor binding domain pocket status in the spike trimer of SARS-CoV-2 variants | |
| Jim Warwicker | |
| Acceso Abierto | |
| Atribución-NoComercial | |
| https://doi.org/10.1101/2021.12.14.472554 | |
| https://www.biorxiv.org/content/10.1101/2021.12.14.472554v1 | |
| Existence of a SARS-CoV-2 spike protein trimer form with closer packing between monomers when receptor binding domains (RBDs) are all down, locked as opposed to closed, has been associated with linoleic acid (LA) binding at neutral pH, or can occur at acidic pH in the absence of LA binding. The relationship between degree of closure of the LA binding pocket of the RBD, and monomer burial in the trimer, is examined for a range of spike protein structures, including those with D614G mutation, and that of the Delta variant (which also carries D614G). Some spike protein structures with this aspartic acid mutation show monomer packing approaching that of the locked form (at neutral pH, without LA binding) for two segments, a third (around the RBD) remains less closely packed. Analysis of other coronavirus RBD structures suggests that mutation of the RBD in spike protein of the Omicron variant could lead to LA binding pocket changes. It is proposed that these changes could lead to one of two consequences for the Omicron variant spike protein (which also has the D614G mutation), at neutral pH and without LA binding, either easier access to a locked form throughout that leads to cooperative transitions between all RBD down and all RBD up, or maintenance of a spike trimer with locked characteristics C-terminal to the RBD at the same time as the RBD is free to transit between down and up states. The situation may also be impacted by spike protein charge mutations in the Omicron lineage that alter pH-dependence around the RBD, in a similar way to the changes induced elsewhere by D614G. | |
| bioRxiv | |
| 14-12-2021 | |
| Preimpreso | |
| www.biorxiv.org | |
| Inglés | |
| Epidemia COVID-19 | |
| Investigadores Público en general | |
| VIRUS RESPIRATORIOS | |
| Versión publicada | |
| publishedVersion - Versión publicada | |
| Aparece en las colecciones: | Artículos científicos |
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| Relationship between monomer packing and receptor binding domain pocket status in the spike trimer of SARS COV2 Variants.pdf | 970.61 kB | Adobe PDF | Visualizar/Abrir |