8WKU

Complex structure of MjHKU4r-CoV-1 spike RBD bound to human CD26

Summary for 8WKU

• Entry DOI: 10.2210/pdb8wku/pdb
• Descriptor: Dipeptidyl peptidase 4 soluble form, MjHKU4r-CoV-1 spike RBD, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (9 entities in total)
• Functional Keywords: mjhku4r-cov-1, spike rbd, human cd26, viral protein/hydrolase, viral protein-hydrolase complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 119696.82

Authors

Zhao, Z.N.,Chai, Y.,Gao, F. (deposition date: 2023-09-28, release date: 2024-06-26, Last modification date: 2024-10-16)

Primary citation

Zhao, Z.,Li, X.,Chai, Y.,Liu, Z.,Wang, Q.,Gao, G.F.
Molecular basis for receptor recognition and broad host tropism for merbecovirus MjHKU4r-CoV-1.
Embo Rep., 25:3116-3136, 2024

PubMed Abstract: A novel pangolin-origin MERS-like coronavirus (CoV), MjHKU4r-CoV-1, was recently identified. It is closely related to bat HKU4-CoV, and is infectious in human organs and transgenic mice. MjHKU4r-CoV-1 uses the dipeptidyl peptidase 4 (DPP4 or CD26) receptor for virus entry and has a broad host tropism. However, the molecular mechanism of its receptor binding and determinants of host range are not yet clear. Herein, we determine the structure of the MjHKU4r-CoV-1 spike (S) protein receptor-binding domain (RBD) complexed with human CD26 (hCD26) to reveal the basis for its receptor binding. Measuring binding capacity toward multiple animal receptors for MjHKU4r-CoV-1, mutagenesis analyses, and homology modeling highlight that residue sites 291, 292, 294, 295, 336, and 344 of CD26 are the crucial host range determinants for MjHKU4r-CoV-1. These results broaden our understanding of this potentially high-risk virus and will help us prepare for possible outbreaks in the future.

PubMed: 38877169
DOI: 10.1038/s44319-024-00169-8

Experimental method

X-RAY DIFFRACTION (3.5 Å)