Sequencing and modeling of anti-DNA immunoglobulin Fv domains. Comparison with crystal structures.
Models for the three-dimensional structures of the combining regions of six DNA-binding antibodies have been derived from the sequence data for their Fv domains presented here. Using the amino acid sequences and the canonical structure classes described by Chothia and Lesk (Chothia, C., and Lesk, A.M. (1987) J. Mol. Biol. 196, 901), model loops were selected from immunoglobulin domains of known structure for five of the six antibody hypervariable regions. Models for the third complementarity-determining region of the heavy chain were constructed from known immunoglobulin loops of similar length and sequence. Comparison of three of the models with the respective crystal structure indicates that this procedure can generate a working model of the antibody combining region that provides useful information on the nature of the interactions between antibodies and nucleic acids. As part of our continuing investigation into the structural basis of antibody-DNA recognition, the observed and predicted models for the combining regions of nucleic acid-binding antibodies have been examined. In general, single strand-specific antibodies have deep clefts where the antigen might bind, whereas duplex-specific antibodies present a relatively flat surface. In addition, on the basis of both sequence and structure, there is little to distinguish autoimmune antibodies from those produced by immunization. Testable hypotheses for how these antibodies might interact with single- and double-stranded nucleic acids are presented.
Barry
M M
MM
Department of Biochemistry, University of Saskatchewan, Saskatoon, Canada.
Mol
C D
CD
Anderson
W F
WF
Lee
J S
JS
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000737:chemistry*; D000918:Antibody Specificity; D001483:Base Sequence; D003196:Computer Graphics; D004247:DNA / Q000276:immunology*; D017931:DNA Primers; D006825:Hybridomas / Q000276:immunology; D007127:Immunoglobulin Constant Regions / Q000096:biosynthesis / Q000737:chemistry; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000737:chemistry; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000737:chemistry; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000737:chemistry*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D004247:DNA