Biology subjects

Arbabian, A.

Publications and source records attributed to Arbabian, A..

2 recordsLinked to original sources

bioRxiv2025

Dipeptidase 1 is a functional receptor for coronavirus PHEV

Coronaviruses of the subgenus Embecovirus include several relevant pathogens such as the human seasonal coronaviruses HKU1 and OC43, bovine coronavirus, and porcine hemagglutinating encephalomyelitis virus (PHEV), among others. While sialic acid is thought to be required for embecovirus entry, protein receptors are unknown in most cases. Here we show that PHEV does not require sialic acid for entry and uses dipeptidase 1 (DPEP1) as a receptor. Cryo-electron microscopy revealed that PHEV, unlike other embecoviruses, samples open and closed conformations of its spike trimer at steady state. We found that the receptor binding domain (RBD) of the PHEV spike shares no detectable sequence homology or receptor usage with those of closely related viruses. In contrast, the X-ray structure of the RBD/DPEP1 complex showed that the elements involved in receptor binding are conserved across embecoviruses, revealing a striking versatility of the RBD to accommodate highly variable sequences that confer novel receptor specificities.

microbiology↗

bioRxiv2024

Structural basis of TMPRSS2 zymogen activation and recognition by the HKU1 seasonal coronavirus

The human seasonal coronavirus HKU1-CoV, which causes common colds worldwide, relies on the sequential binding to a cell-surface glycan and to TMPRSS2 for entry into target cells. TMPRSS2 is a cell surface protease synthesized as a zymogen that undergoes autolytic activation to process its substrates. Several respiratory viruses - in particular coronaviruses - use TMPRSS2 for proteolytic priming of their surface spike protein to drive membrane fusion upon receptor binding. We describe the crystal structure of the HKU1-CoV receptor binding domain in complex with TMPRSS2, showing that it recognizes residues lining the catalytic groove. Combined mutagenesis of interface residues and comparison across species highlight positions 417 and 469 as determinants of HKU1-CoV host tropism. The structure of a receptor- blocking nanobody in complex with zymogen or activated TMPRSS2 further provides the structural basis of the TMPRSS2 activating conformational change, altering loops recognized by HKU1-CoV and dramatically increasing its binding affinity.

biochemistry↗