Cryo-EM structure of rhinovirus C15a bound to its cadherin-related protein 3 receptor

Proceedings of the National Academy of Sciences of the United States of America
Yingyuan SunAnn C Palmenberg

Abstract

Infection by Rhinovirus-C (RV-C), a species of Picornaviridae Enterovirus, is strongly associated with childhood asthma exacerbations. Cellular binding and entry by all RV-C, which trigger these episodes, is mediated by the first extracellular domain (EC1) of cadherin-related protein 3 (CDHR3), a surface cadherin-like protein expressed primarily on the apical surfaces of ciliated airway epithelial cells. Although recombinant EC1 is a potent inhibitor of viral infection, there is no molecular description of this protein or its binding site on RV-C. Here we present cryo-electron microscopy (EM) data resolving the EC1 and EC1+2 domains of human CDHR3 complexed with viral isolate C15a. Structure-suggested residues contributing to required interfaces on both EC1 and C15a were probed and identified by mutagenesis studies with four different RV-C genotypes. In contrast to most other rhinoviruses, which bind intercellular adhesion molecule 1 receptors via a capsid protein VP1-specific fivefold canyon feature, the CDHR3 EC1 contacts C15a, and presumably all RV-Cs, in a unique cohesive footprint near the threefold vertex, encompassing residues primarily from viral protein VP3, but also from VP1 and VP2. The EC1+2 footprint on C15a is sim...Continue Reading

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Citations

Jan 28, 2021·Viruses·Woonghee LeeAnn C Palmenberg
Feb 6, 2021·Cellular Microbiology·Sagarika DashDibyendu Samanta
Dec 29, 2020·American Journal of Respiratory and Critical Care Medicine·Timothy ChoiYury A Bochkov

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