9EA0
Structure of the prefusion HKU5-19s Spike trimer (conformation 1)
Summary for 9EA0
| Entry DOI | 10.2210/pdb9ea0/pdb |
| EMDB information | 47823 |
| Descriptor | Spike glycoprotein, LINOLEIC ACID, alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[2-acetamido-2-deoxy-beta-D-glucopyranose-(1-2)-alpha-D-mannopyranose-(1-3)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (11 entities in total) |
| Functional Keywords | mers-related hku5 coronaviruses, mersr-cov, spike glycoprotein, fusion protein, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein |
| Biological source | Pipistrellus bat coronavirus HKU5 |
| Total number of polymer chains | 3 |
| Total formula weight | 481024.35 |
| Authors | Park, Y.J.,Gen, R.,Seattle Structural Genomics Center for Infectious Disease (SSGCID),Veesler, D. (deposition date: 2024-11-09, release date: 2025-02-26, Last modification date: 2025-04-02) |
| Primary citation | Park, Y.J.,Liu, C.,Lee, J.,Brown, J.T.,Ma, C.B.,Liu, P.,Gen, R.,Xiong, Q.,Zepeda, S.K.,Stewart, C.,Addetia, A.,Craig, C.J.,Tortorici, M.A.,Alshukairi, A.N.,Starr, T.N.,Yan, H.,Veesler, D. Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses. Cell, 188:1711-1728.e21, 2025 Cited by PubMed Abstract: DPP4 was considered a canonical receptor for merbecoviruses until the recent discovery of African bat-borne MERS-related coronaviruses using ACE2. The extent and diversity of ACE2 utilization among merbecoviruses and their receptor species tropism remain unknown. Here, we reveal that HKU5 enters host cells utilizing Pipistrellus abramus (P.abr) and several non-bat mammalian ACE2s through a binding mode distinct from that of any other known ACE2-using coronaviruses. We defined the molecular determinants of receptor species tropism and identified a single amino acid mutation enabling HKU5 to utilize human ACE2, providing proof of principle for machine-learning-assisted outbreak preparedness. We show that MERS-CoV and HKU5 have markedly distinct antigenicity and identified several HKU5 inhibitors, including two clinical compounds. Our findings profoundly alter our understanding of coronavirus evolution, as several merbecovirus clades independently evolved ACE2 utilization, and pave the way for developing countermeasures against viruses poised for human emergence. PubMed: 39922192DOI: 10.1016/j.cell.2024.12.032 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2 Å) |
Structure validation
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