The cellular receptor to human rhinovirus 2 binds around the 5-fold axis and not in the canyon: a structural view

Abstract
Human rhinovirus serotype 2 (HRV2) belongs to the minor group of HRVs that bind to members of the LDL‐receptor family including the very low density lipoprotein (VLDL)‐receptor (VLDL‐R). We have determined the structures of the complex between HRV2 and soluble fragments of the VLDL‐R to 15 Å resolution by cryo‐electron microscopy. The receptor fragments, which include the first three ligand‐binding repeats of the VLDL‐R (V1–3), bind to the small star‐shaped dome on the icosahedral 5‐fold axis. This is in sharp contrast to the major group of HRVs where the receptor site for ICAM‐1 is located at the base of a depression around each 5‐fold axis. Homology models of the three domains of V1–3 were used to explore the virus–receptor interaction. The footprint of VLDL‐R on the viral surface covers the BC‐ and HI‐loops on VP1.