Systematic replacement of amino acid residues within an Arg-Gly-Asp-containing loop of foot-and-mouth disease virus and effect on cell recognition.
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.
Mateu
M G
MG
Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain.
Valero
M L
ML
Andreu
D
D
Domingo
E
E
D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D005537:Aphthovirus / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D002460:Cell Line; D006224:Cricetinae; D008561:Membrane Fusion / Q000235:genetics*; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics*; D010455:Peptides / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
D000956:Antigens, Viral; D009842:Oligopeptides; D010455:Peptides; C047981:arginyl-glycyl-aspartic acid