Abstract
The conserved Arg-Gly-Asp (RGD) motif found in a hypervariable, mobile antigenic loop of foot-and-mouth disease virus (FMDV) is critically involved in virus attachment to cells by binding to an integrin, probably related to alphavbeta3. Here we describe (i) the synthesis of 241 15-mer peptides, which represent this loop of FMDV (isolate C-S8c1) and single variants in which each amino acid residue was replaced by 16 others and (ii) the inhibitory activity of these peptides on the ability of FMDV C-S8c1 to recognize and infect susceptible cells. This approach has allowed a first detailed evaluation of the specificity of each residue within a RGD-containing protein loop on cell recognition. The results indicate that, in addition to the exquisitely specific RGD triplet, two highly conserved Leu residues located at positions +1 and +4 downstream of the RGD and, to a lesser extent, the residue at position +2 are the only critical and specific determinants within the loop in promoting cell recognition of a viral ligand. The results support the proposal that, in spite of their involvement in antibody recognition, RGD and other FMDV loop residues are remarkably conserved because of their essential role in cell recognition.
Highlights
Two highly conserved Leu residues located at positions ؉1 and ؉4 downstream of the RGD and, to a lesser extent, the residue at position ؉2 are the only critical and specific determinants within the loop in promoting cell recognition of a viral ligand
The results indicate that, in addition to the RGD triplet, two highly conserved Leu residues located at positions ϩ1 and ϩ4 downstream of the RGD motif and the residue at position ϩ2 are the
Because of the availability of the three-dimensional structure of peptide A15 complexed to an antibody (Fig. 1), we have chosen this peptide as a model of the G-H loop to study the role of amino acid residues within this segment in determining the ability of foot-and-mouth disease virus (FMDV) to recognize and infect susceptible cells
Summary
Two highly conserved Leu residues located at positions ؉1 and ؉4 downstream of the RGD and, to a lesser extent, the residue at position ؉2 are the only critical and specific determinants within the loop in promoting cell recognition of a viral ligand. The use of RGD-containing peptides (e.g. acids), which reproduced the G-H loop of serotype C viruses, inhibited very effectively FMDV infectivity (IC50 about 0.8 M) and attachment to cells [16].
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