Receptor-binding loops in alphacoronavirus adaptation and evolution

• DOI: 10.1038/s41467-017-01706-x
• Publication Date: 2017-11-17T18:59:39Z
• Authors: Alan H. M. Wong; Aidan C. A. Tomli...; Dongxia Zhou; Malathy Satkunarajah; Kevin Chen; Chetna Sharon; Marc Desforges; Pierre J. Talbot; James M. Rini
• Keywords: Ectodomain; Coronavirus

RNA viruses are characterized by a high mutation rate, buffer against environmental change. Nevertheless, the means which random improves viral fitness is not well characterized. Here we report X-ray crystal structure of receptor-binding domain (RBD) human coronavirus, HCoV-229E, in complex with ectodomain its receptor, aminopeptidase N (APN). Three extended loops solely responsible for receptor binding and evolution HCoV-229E close relatives accompanied changing loop-receptor interactions. Phylogenetic analysis shows that natural loop variation observed defines six RBD classes whose have successively replaced each other population over past 50 years. These differ their affinity APN ability to bind an neutralizing antibody. Together, our results provide model alphacoronavirus adaptation based on use binding.