8opn | pdb_00008opn
Human Coronavirus HKU1 spike glycoprotein in complex with an alpha2,8-linked 9-O-acetylated disialoside (1-up state)
Structural highlights
FunctionE0YJ44_CVHK1 Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Spike protein S2: 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]GCN4_YEAST Is a transcription factor that is responsible for the activation of more than 30 genes required for amino acid or for purine biosynthesis in response to amino acid or purine starvation. Binds and recognize the DNA sequence: 5'-TGA[CG]TCA-3'. Publication Abstract from PubMedCoronavirus spike proteins mediate receptor binding and membrane fusion, making them prime targets for neutralizing antibodies. In the cases of severe acute respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus, spike proteins transition freely between open and closed conformations to balance host cell attachment and immune evasion(1-5). Spike opening exposes domain S1(B), allowing it to bind to proteinaceous receptors(6,7), and is also thought to enable protein refolding during membrane fusion(4,5). However, with a single exception, the pre-fusion spike proteins of all other coronaviruses studied so far have been observed exclusively in the closed state. This raises the possibility of regulation, with spike proteins more commonly transitioning to open states in response to specific cues, rather than spontaneously. Here, using cryogenic electron microscopy and molecular dynamics simulations, we show that the spike protein of the common cold human coronavirus HKU1 undergoes local and long-range conformational changes after binding a sialoglycan-based primary receptor to domain S1(A). This binding triggers the transition of S1(B) domains to the open state through allosteric interdomain crosstalk. Our findings provide detailed insight into coronavirus attachment, with possibilities of dual receptor usage and priming of entry as a means of immune escape. Sialoglycan binding triggers spike opening in a human coronavirus.,Pronker MF, Creutznacher R, Drulyte I, Hulswit RJG, Li Z, van Kuppeveld FJM, Snijder J, Lang Y, Bosch BJ, Boons GJ, Frank M, de Groot RJ, Hurdiss DL Nature. 2023 Dec;624(7990):201-206. doi: 10.1038/s41586-023-06599-z. Epub 2023 , Oct 4. PMID:37794193[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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