Structural studies of two rhinovirus serotypes complexed with fragments oftheir cellular receptor

Two human rhinovirus serotypes complexed with two- and five-domain soluble fragments of the cellular receptor, intercellular adhesion molecule-1, have been investigated by X-ray crystallographic analyses of the individual com ponents and by cryo-electron microscopy of the complexes. The three-dimensi onal image reconstructions provide a molecular envelope within which the cr ystal structures of the viruses and the receptor fragments can be positione d with accuracy. The N-terminal domain of the receptor binds to the rhinovi rus 'canyon' surrounding the icosahedral 5-fold axes. Fitting of molecular models into the image reconstruction density identified the residues on the virus that interact with those on the receptor surface, demonstrating comp lementarity of the electrostatic patterns for the tip of the N-terminal rec eptor domain and the floor of the canyon, The complexes seen in the image r econstructions probably represent the first stage of a multistep binding pr ocess. A mechanism is proposed for the subsequent viral uncoating process.