Interaction of the poliovirus receptor with poliovirus

Abstract

The structure of the extracellular, three-domain poliovirus receptor (CD155) complexed with poliovirus (serotype 1) has been determined to 22-A resolution by means of cryo-electron microscopy and three-dimensional image-reconstruction techniques. Density corresponding to the receptor was isolated in a difference electron density map and fitted with known structures, homologous to those of the three individual CD155 Ig-like domains. The fit was confirmed by the location of carbohydrate moieties in the CD155 glycoprotein, the conserved properties of elbow angles in the structures of cell surface molecules with Ig-like folds, and the concordance with prior results of CD155 and poliovirus mutagenesis. CD155 binds in the poliovirus "canyon" and has a footprint similar to that of the intercellular adhesion molecule-1 receptor on human rhinoviruses. However, the orientation of the long, slender CD155 molecule relative to the poliovirus surface is quite different from the orientation of intercellular adhesion molecule-1 on rhinoviruses. In addition, the residues that provide specificity of recognition differ for the two receptors. The principal feature of receptor binding common to these two picornaviruses is the site in the canyon at which binding occurs. This site may be a trigger for initiation of the subsequent uncoating step required for viral infection.

Figure 1

Comparison of the mature structures of ICAM-1, the receptor for the major group of rhinoviruses, with the human PV receptor (hCD155), the monkey PV receptor (mCD155), and the murine poliovirus receptor-related protein 2 (mPRR2). Sites of glycosylation are indicated by shaded circles. The number of amino acids is shown for each domain.

Figure 2

The C_α backbone of domain D1 of CD155 based on its homology to protein zero. Shown is the nomenclature of the β-strands, the two sites of potential glycosylation, and strategically numbered residues. Residues that were found to make contact with the north rim of the canyon are colored green, with the south rim yellow, with the floor blue, and with the additional surface area red. Potential glycosylation sites are colored black.

Figure 3

(a) Stereoview of the cryo-EM reconstruction showing the complex of PV1(M) with human CD155. The outline of one geometric icosahedral asymmetric unit is shown. Note that the receptor leans towards the southeast. (b) Stereoview of the cryo-EM reconstruction showing the complex of HRV16 with its ICAM-1 receptor (from ref. 28). The outline of one geometric icosahedral asymmetric unit is shown. Note that the receptor leans towards the southwest. (c) Stereoview of a cryo-EM reconstruction of PV, also showing the geometric icosahedral asymmetric unit. Note the asymmetric shape of the canyon with its most southerly point slightly east of center (arrow) and the smaller peak southwest of the canyon (arrow). These features establish the correct hand of the reconstructions in a and b and are consistent with the x-ray results, where the absolute hand is known. (d) Density (green) representing one CD155 molecule (black) fitted with the C_α backbone structure of the closest homologous structures found in the PDB for each of the three domains. Shown also is the difference map (blue) between the cryo-EM density and the unglycosylated CD155 model to show the sites of glycosylation. The potential glycosylation sites are shown on the CD155 backbone (red).

Figure 4

Sequence alignment of human CD155 domain D1 with protein zero. Secondary structural elements are indicated, and potential glycosylation sites are marked with an *. Residues implicated in binding to PV are marked with an X (15, 16) and a + (14, 17, 38) in the lines above the residue numbers. The color code for residues that are involved in binding to PV is the same as in Fig. 2.

Figure 5

Stereoview of CD155 (yellow) docked onto PV. VP1, VP2, and VP3 coloring is blue, green, and red, respectively.

Figure 6

The footprint of the CD155 on the PV surface, defined by those residues on the viral surface that have any atoms within 4 Å of any atom in the receptor. (Inset) One icosahedral asymmetric unit with the footprint outlined and the limits of the canyon. (Left) The footprint on the virus (the canyon has a black outline). (Right) The residues of CD155 in contact with the viral surface. Each residue is colored in accordance with its chemical properties: green, hydrophobic; yellow, hydrophilic; red, acidic; and blue, basic.