Sequence and structure of human rhinoviruses reveal the basis of receptor discrimination - PubMed (original) (raw)

Sequence and structure of human rhinoviruses reveal the basis of receptor discrimination

Marketa Vlasak et al. J Virol. 2003 Jun.

Abstract

The sequences of the capsid protein VP1 of all minor receptor group human rhinoviruses were determined. A phylogenetic analysis revealed that minor group HRVs were not more related to each other than to the nine major group HRVs whose sequences are known. Examination of the surface exposed amino acid residues of HRV1A and HRV2, whose X-ray structures are available, and that of three-dimensional models computed for the remaining eight minor group HRVs indicated a pattern of positively charged residues within the region, which, in HRV2, was shown to be the binding site of the very-low-density lipoprotein (VLDL) receptor. A lysine in the HI loop of VP1 (K224 in HRV2) is strictly conserved within the minor group. It lies in the middle of the footprint of a single repeat of the VLDL receptor on HRV2. Major group virus serotypes exhibit mostly negative charges at the corresponding positions and do not bind the negatively charged VLDL receptor, presumably because of charge repulsion.

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Figures

FIG. 1.

FIG. 1.

Strategy for the reverse transcriptase PCR sequencing of the genomic HRV region encoding VP1. The primers used are listed in Table 1.

FIG. 2.

FIG. 2.

Neighbor-joining tree of 10 minor and 9 major group HRVs based on VP1 amino acid sequences. The analysis was carried out with ClustalW. Note the grouping of HRV1A and -B; -29, -31, -44, -47, and -62; and -2, -30, and -49. Minor group HRVs are shown in boldface; classification as species A and B is also indicated.

FIG. 3.

FIG. 3.

Structural alignment of HRV VP1 sequences of the BC, DE, and HI loops, taking into account all amino acid residues within 12 Å (shaded) from K224 in HRV2 and from the equivalent amino acid residues in the other HRVs. K224 conserved in all minor group HRVs and the corresponding residues in major group HRVs are highlighted. Residues within the footprint of V3 on HRV2 (Neumann et al., submitted) are underlined. Note that residues of the neighboring VP1 are also close to K224 but are in fact not in the footprint of the single repeat.

FIG. 4.

FIG. 4.

Road maps of all minor group HRVs (HRV1A, -1B, -2, -29, -30, -31, -44, -47, -49, and -62), indicated in blue and boldface, and 9 major group HRV2 (HRV3, -9, -14, -15, -16, -50, -85, and -89), indicated in black, including VP1 amino acid residues 35 Å from the fivefold axis. Blue, basic; red, acidic; yellow, hydrophobic; and green, hydrophilic uncharged; His is colored light blue. For orientation, the size of the entire asymmetric unit is indicated with a triangle in HRV2. The position of the lysine in the HI loop of minor group HRVs is colored black and is specified with an arrow. Note the presence of a lysine in the HI loop of HRV85.

FIG. 5.

FIG. 5.

Surface potential of 10 minor group (bold yellow lettering) and 9 major group HRVs (plain white lettering) centered on the position of binding of V3 on HRV2 as delineated in the stereo drawing of an HRV2 pentamer (top). Surface potentials were calculated with Swiss-PdbViewer by using the available X-ray coordinates and the coordinates predicted by SwissModel. For the models the same scale (blue, 2.5, positive; and red, −2.5, negative) was used. Amino acids within 12 Å from K224 in HRV2 (indicated by O) or from the amino acids at the equivalent position (see structural alignment in Fig. 3) are displayed. The view is from the side onto the north wall of the canyon and is centered on K224 as indicated on the top. This view avoids the underestimation of the exposed surfaces by the road map due to the steep descent at the canyon.

FIG. 6.

FIG. 6.

Neighbor-joining tree of 10 minor and 9 major group HRVs based on the VP1 amino acid sequences within a sphere around K224 (HRV2) with a 12-Å radius. Sequence fragments were joined and treated as single sequences comprising parts of the BC, the DE, and the HI loops contributed from the two symmetry-related VP1 molecules. The analysis was carried out with ClustalW. Note that the clusters of serotypes HRV1A and -B; -29, -31, -44, -47, and -62; and -2, -30, and -49 are the same as in Fig. 2, where the entire VP1 was analyzed. Minor group HRVs are shown in boldface; classification as species A and B is also indicated.

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