7y71
From Proteopedia
SARS-CoV-2 spike glycoprotein trimer complexed with Fab fragment of anti-RBD antibody E7
Structural highlights
FunctionSPIKE_SARS2 attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099][1] [2] [3] 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 PubMedThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo-electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure-dependent epitope. Potent pan huACE2-dependent sarbecovirus neutralizing monoclonal antibodies isolated from a BNT162b2-vaccinated SARS survivor.,Chia WN, Tan CW, Tan AWK, Young B, Starr TN, Lopez E, Fibriansah G, Barr J, Cheng S, Yeoh AY, Yap WC, Lim BL, Ng TS, Sia WR, Zhu F, Chen S, Zhang J, Kwek MSS, Greaney AJ, Chen M, Au GG, Paradkar PN, Peiris M, Chung AW, Bloom JD, Lye D, Lok S, Wang LF Sci Adv. 2023 Jul 28;9(30):eade3470. doi: 10.1126/sciadv.ade3470. Epub 2023 Jul , 26. PMID:37494438[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Homo sapiens | Large Structures | Au GG | Barr J | Bloom JD | Chen M | Chen S | Cheng S | Chia WN | Chung AW | Fibriansah G | Greaney AJ | Lim BL | Lok SM | Lopez E | Lye D | Ng TS | Paradkar P | Peiris M | Sia WR | Starr TN | Tan AWK | Tan CW | Wang LF | Yap WC | Yeoh AYY | Young B | Zhang J | Zhu F
