An improved model of association for VH-VL immunoglobulin domains: asymmetries between VH and VL in the packing of some interface residues.
The antibody-binding site is formed as a result of the association between VH and VL domains. Several studies have shown that this association plays an important role in the mechanism of antigen-antibody interaction (Stanfield et al. Structure 1: 83-93, 1993). Considering this, we propose that variations in the VH-VL association are part of the diversification strategy of the antibody repertoires. Previously, a model of association for VH-VL domains based on geometrical characteristics of the packing at the interface was developed by Chothia et al. (J. Mol. Biol. 186: 61-663, 1985). This model includes a common association form for antibodies and a three-layer structure for the interface. In the present work, a complementary model is introduced to account for the general geometrical restrictions of the VH-VL interface, and particular arrangements related to the chemical properties or the side-chain orientations of participating residues. Groups of residues assume common side-chain orientations, which are apparently related to particular functions of different interface zones. Analyses of amino acid usage and network are in agreement with the side-chain orientation patterns. Based on these observations, a three-zone model has evolved to illuminate geometrical and functional restrictions acting over the VH-VL interface. Additionally, this study has revealed the asymmetrical relationships between VH and VL residues important for the association of the two domains.
Vargas-Madrazo
Enrique
E
Instituto de Investigaciones Biológicas, Universidad Veracruzana, Xalapa, Veracruz, México. evargas@uv.mx
Paz-García
Enrique
E
D000818:Animals; D001666:Binding Sites, Antibody; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry*; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D008958:Models, Molecular; D011487:Protein Conformation
D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains