Dengue virus envelope glycoprotein structure: New insight into its interactions during viral entry

摘要

A major step in understanding the molecular interactions that lead to entry of enveloped viruses into their target cells is obtaining structural information on the viral surface glycoproteins at the atomic level. In addition to carrying the main antigenic determinants of the virus, these proteins are responsible for the major steps involved in the entry process, which involve receptor recognition and fusion between viral and cellular membranes. A huge step forward in the field was made >20 years ago, when the laboratories of Don Wiley and John Skehel obtained the crystal structure of the influenza virus hemagglutinin (HA) , which carries both receptor-binding and membrane fusion functions. Since then, the x-ray structures of relatively few soluble ectodomains of viral glycoproteins have been determined, compared to the exponential increase of protein structures deposited in the Protein Data Bank in the same period. In particular, structural information on viral envelope proteins combining both receptor-binding and membrane fusion functions is very scarce. Over the years, only the structures of the tick-borne encephalitis (TBE) flavivirus major envelope (E) protein and of the influenza C virus HA-esterase glycoprotein were added to the database. In this issue of PNAS, Modis et al. (4) report the crystal structure of the E protein from dengue virus, a mosquito-borne flavivirus responsible for the highest rate of disease and mortality among members of this viral genus. This structure is therefore a very important addition to the current repertoire.