Three-dimensional structure of poliovirus receptor bound to poliovirus

Poliovirus initiates infection by binding to its cellular receptor (Pvr). W e have studied this interaction by using cryoelectron microscopy to determi ne the structure, at 21-Angstrom resolution, of poliovirus complexed with a soluble form of its receptor (sPvr). This density map aided construction o f a homology-based model of sPvr and, in conjunction with the known crystal structure of the virus, allowed delineation of the binding site. The virio n does not change significantly in structure on binding sPvr in short incub ations at 4 degrees C. We infer that the binding configuration visualized r epresents the initial interaction that is followed by structural changes in the virion as infection proceeds. sPvr is segmented into three well-define d Ig-like domains. The two domains closest to the virion (domains 1 and 2) are aligned and rigidly connected, whereas domain 3 diverges at an angle of approximate to 60 degrees. Two nodules of density on domain 2 are identifi ed as glycosylation sites. Domain 1 penetrates the "canyon" that surrounds the 5-fold protrusion on the capsid surface, and its binding site involves all three major capsid proteins. The inferred pattern of virus-sPvr interac tions accounts for most mutations that affect the binding of Pvr to poliovi rus.