Crystal structure of Bruton's tyrosine kinase domain suggests a novel pathway for activation and provides insights into the molecular basis of X-linked agammaglobulinemia

J Biol Chem. 2001 Nov 2;276(44):41435-43. doi: 10.1074/jbc.M104828200. Epub 2001 Aug 29.


Bruton's tyrosine kinase is intimately involved in signal transduction pathways regulating survival, activation, proliferation, and differentiation of B lineage lymphoid cells. Mutations in the human btk gene are the cause of X-linked agammaglobulinemia, a male immune deficiency disorder characterized by a lack of mature, immunoglobulin-producing B lymphocytes. We have determined the x-ray crystal structure of the Bruton's tyrosine kinase kinase domain in its unphosphorylated state to a 2.1 A resolution. A comparison with the structures of other tyrosine kinases and a possible mechanism of activation unique to Bruton's tyrosine kinase are provided.

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / genetics*
  • Animals
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Enzyme Activation
  • Genetic Linkage*
  • Humans
  • Mice
  • Models, Molecular
  • Mutation, Missense
  • Phosphorylation
  • Protein Conformation
  • Protein-Tyrosine Kinases / chemistry*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / isolation & purification
  • Protein-Tyrosine Kinases / metabolism
  • Tyrosine / metabolism
  • X Chromosome*


  • Tyrosine
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Btk protein, mouse