Crystal structure of a shark single-domain antibody V region in complex with lysozyme

Science. 2004 Sep 17;305(5691):1770-3. doi: 10.1126/science.1101148. Epub 2004 Aug 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Complementarity Determining Regions / chemistry
  • Crystallography, X-Ray
  • Dimerization
  • Drug Combinations
  • Evolution, Molecular
  • Genes, Immunoglobulin
  • Immunoglobulin Heavy Chains / chemistry*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Heavy Chains / metabolism
  • Immunoglobulin Variable Region / chemistry*
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / immunology
  • Immunoglobulin Variable Region / metabolism
  • Immunoglobulins / chemistry*
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology
  • Immunoglobulins / metabolism
  • Meglumine
  • Models, Molecular
  • Muramidase / chemistry*
  • Muramidase / immunology
  • Muramidase / metabolism
  • Protein Conformation
  • Protein Folding
  • Protein Structure, Tertiary
  • Receptors, Antigen / chemistry*
  • Receptors, Antigen / genetics
  • Receptors, Antigen / immunology
  • Receptors, Antigen / metabolism
  • Sharks / immunology*
  • Tetrahydropapaveroline / analogs & derivatives*

Substances

  • Complementarity Determining Regions
  • Drug Combinations
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulins
  • Receptors, Antigen
  • nurse shark antigen receptor
  • Tetrahydropapaveroline
  • UTEN
  • Meglumine
  • hen egg lysozyme
  • Muramidase

Associated data

  • PDB/1SQ2
  • PDB/1T6V