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==HuCoV-HKU1 C S 2P in complex with H501-018 Fab (State 1, global cryoEM)==
<StructureSection load='9ygn' size='340' side='right'caption='[[9ygn]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ygn]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_coronavirus_HKU1_(isolate_N5) Human coronavirus HKU1 (isolate N5)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9YGN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9YGN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9ygn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ygn OCA], [https://pdbe.org/9ygn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ygn RCSB], [https://www.ebi.ac.uk/pdbsum/9ygn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ygn ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/SPIKE_CVHN5 SPIKE_CVHN5] S1 attaches the virion to the cell membrane by interacting with cell receptors, initiating the infection.  S2 is a class I viral fusion protein. Under the current model, the protein has at least 3 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. Presumably interacts with target cell lipid raft after cell attachment (By similarity).
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== Publication Abstract from PubMed ==
Endemic human coronaviruses (HCoVs), like HCoV-HKU1, account for ~30% of common cold/year and can cause serious upper and lower respiratory infections, yet no licensed vaccines target HCoVs. In fact, little is known about HCoV-HKU1's antigenic landscape. Thus, we characterized key interactions between HCoV-HKU1 spike (S) with monoclonal antibodies (mAbs) isolated from pre-pandemic HCoV-HKU1 convalescent PBMCs. We isolated 14 mAbs, which bound distinct S regions: receptor binding domain (RBD), N-terminal domain (NTD), and S2 subunit. Structural and functional studies revealed three groups of RBD-specific mAbs targeting diverse footprints within and around the TMPRSS2 receptor binding site, exemplified by: (1) The most potently neutralizing mAb, H501-022 (IC(50) = 0.01 mug/mL), which recognizes the TMPRSS2 binding motif, thereby blocking receptor engagement; (2) mAb H501-008 (IC(50) = 0.05 mug/mL) that binds a conserved, cross-reactive epitope outside of the TMPRSS2 binding site that is shared with HCoV-OC43; and (3) H501-018 (IC(50) = 0.28 mug/mL) that recognizes both "up" and "down" RBD conformations at a distinct, non-overlapping site outside of the TMPRSS2 binding motif, distinguishing itself from H501-022 and H501-008, which bind exclusively to the "up" RBD conformation. These mAbs represent the first type-specific HCoV-HKU1 mAbs isolated from a convalescent donor. Our findings provide molecular insight into HCoV-HKU1 antibody recognition and neutralization mechanisms, importantly highlighting antigenic differences comparing HCoVs and pandemic CoVs - a critical step towards advancing universal CoV vaccine design.

Human Coronavirus HKU1 Neutralizing Monoclonal Antibodies Target Diverse Epitopes Within and Around the TMPRSS2 Receptor Binding Site.,Wang L, Joseph J, Vasquez S, Wrapp D, Sheahan TP, Dzuvor CKO, Rosen O, Kirchdoerfer RN, Abiona OM, Hammond C, Shi W, Moak SP, Kong WP, Zhang Y, Eso MR, Brown AJ, Ward AB, Baric R, McLellan JS, Pierson TC, Mascola J, Graham BS, Yassine HM, Barnes CO, Corbett-Helaire KS bioRxiv [Preprint]. 2025 Oct 30:2025.10.29.685445. doi: , 10.1101/2025.10.29.685445. PMID:41279056<ref>PMID:41279056</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 9ygn" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Barnes CO]]
[[Category: Vasquez S]]