Crystal structure of a shark single-domain antibody V region in complex with lysozyme.
Cartilaginous fish are the phylogenetically oldest living organisms known to possess components of the vertebrate adaptive immune system. Key to their immune response are heavy-chain, homodimeric immunoglobulins called new antigen receptors (IgNARs), in which the variable (V) domains recognize antigens with only a single immunoglobulin domain, akin to camelid heavy-chain V domains. The 1.45 angstrom resolution crystal structure of the type I IgNAR V domain in complex with hen egg-white lysozyme (HEL) reveals a minimal antigen-binding domain that contains only two of the three conventional complementarity-determining regions but still binds HEL with nanomolar affinity by means of a binding interface comparable in size to conventional antibodies.
Department of Molecular Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Robyn L
RL
Stanfield
Helen
H
Dooley
Martin F
MF
Flajnik
Ian A
IA
Wilson
D000818:Animals; D022801:Complementarity Determining Regions / Q000737:chemistry; D018360:Crystallography, X-Ray; D019281:Dimerization; D004338:Drug Combinations; D019143:Evolution, Molecular; D005803:Genes, Immunoglobulin; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008536:Meglumine; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011946:Receptors, Antigen / Q000737:chemistry* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012754:Sharks / Q000276:immunology*; D013765:Tetrahydropapaveroline / Q000031:analogs & derivatives*
D022801:Complementarity Determining Regions; D004338:Drug Combinations; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007136:Immunoglobulins; D011946:Receptors, Antigen; C092388:nurse shark antigen receptor; D013765:Tetrahydropapaveroline; C030644:UTEN; D008536:Meglumine; C421864:hen egg lysozyme; D009113:Muramidase