Three-dimensional structure of poliovirus receptor bound to poliovirus.
Poliovirus initiates infection by binding to its cellular receptor (Pvr). We have studied this interaction by using cryoelectron microscopy to determine the structure, at 21-A resolution, of poliovirus complexed with a soluble form of its receptor (sPvr). This density map aided construction of a homology-based model of sPvr and, in conjunction with the known crystal structure of the virus, allowed delineation of the binding site. The virion does not change significantly in structure on binding sPvr in short incubations at 4 degrees C. We infer that the binding configuration visualized represents the initial interaction that is followed by structural changes in the virion as infection proceeds. sPvr is segmented into three well-defined 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 approximately 60 degrees. Two nodules of density on domain 2 are identified 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 interactions accounts for most mutations that affect the binding of Pvr to poliovirus.
Belnap
D M
DM
Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
McDermott
B M
BM
Filman
D J
DJ
Cheng
N
N
Trus
B L
BL
Zuccola
H J
HJ
Racaniello
V R
VR
Hogle
J M
JM
Steven
A C
AC
D000595:Amino Acid Sequence; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D006031:Glycosylation; D007091:Image Processing, Computer-Assisted; D008565:Membrane Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D017955:Poliovirus / Q000737:chemistry* / Q000648:ultrastructure; D011991:Receptors, Virus / Q000737:chemistry* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000737:chemistry
D008565:Membrane Proteins; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; C066100:poliovirus receptor