1btk
From Proteopedia
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PH DOMAIN AND BTK MOTIF FROM BRUTON'S TYROSINE KINASE MUTANT R28C
Overview
Bruton's tyrosine kinase (Btk) is an enzyme which is involved in, maturation of B cells. It is a target for mutations causing X-linked, agammaglobulinaemia (XLA) in man. We have determined the structure of the, N-terminal part of Btk by X-ray crystallography at 1.6 A resolution. This, part of the kinase contains a pleckstrin homology (PH) domain and a Btk, motif. The structure of the PH domain is similar to those published, previously: a seven-stranded bent beta-sheet with a C-terminal, alpha-helix. Individual point mutations within the Btk PH domain which, cause XLA can be classified as either structural or functional in the, light of the three-dimensional structure and biochemical data. All, functional mutations cluster into the positively charged end of the, molecule around the predicted binding site for phosphatidylinositol, lipids. It is likely that these mutations inactivate the Btk pathway in, cell signalling by reducing its affinity for inositol phosphates, which, causes a failure in translocation of the kinase to the cell membrane. A, small number of signalling proteins contain a Btk motif that always, follows a PH domain in the sequence. This small module has a novel fold, which is held together by a zinc ion bound by three conserved cysteines, and a histidine. The Btk motif packs against the second half of the, beta-sheet of the PH domain, forming a close contact with it. Our, structure opens up new ways to study the role of the PH domain and Btk, motif in the cellular function of Btk and the molecular basis of its, dysfunction in XLA patients.
About this Structure
1BTK is a Single protein structure of sequence from Homo sapiens with ZN and NA as ligands. Active as Transferred entry: 2.7.10.1 and 2.7.10.2, with EC number 2.7.1.112 Structure known Active Sites: ZN1 and ZN2. Full crystallographic information is available from OCA.
Reference
Structure of the PH domain and Btk motif from Bruton's tyrosine kinase: molecular explanations for X-linked agammaglobulinaemia., Hyvonen M, Saraste M, EMBO J. 1997 Jun 16;16(12):3396-404. PMID:9218782
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