Molecular recognition by a binary code.
Functional antibodies were obtained from a library of antigen-binding sites generated by a binary code restricted to tyrosine and serine. An antibody raised against human vascular endothelial growth factor recognized the antigen with high affinity (K(D)=60 nM) and high specificity in cell-based assays. The crystal structure of another antigen binding fragment in complex with its antigen (human death receptor DR5) revealed the structural basis for this minimalist mode of molecular recognition. Natural antigen-binding sites are enriched for tyrosine and serine, and we show that these amino acid residues are intrinsically well suited for molecular recognition. Furthermore, these results demonstrate that molecular recognition can evolve from even the simplest chemical diversity.
Fellouse
Frederic A
FA
Department of Protein Engineering, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA.
Li
Bing
B
Compaan
Deanne M
DM
Peden
Andrew A
AA
Hymowitz
Sarah G
SG
Sidhu
Sachdev S
SS
D000595:Amino Acid Sequence; D000906:Antibodies / Q000737:chemistry / Q000276:immunology; D000918:Antibody Specificity; D000941:Antigens / Q000276:immunology; D001666:Binding Sites, Antibody; D003461:Crystallography; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000276:immunology; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D019151:Peptide Library; D011487:Protein Conformation; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D012694:Serine / Q000737:chemistry / Q000276:immunology*; D014443:Tyrosine / Q000737:chemistry / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D007140:Immunoglobulin Fab Fragments; D019151:Peptide Library; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C505639:TNFRSF10B protein, human; D042461:Vascular Endothelial Growth Factor A; D014443:Tyrosine; D012694:Serine