Conformation of full-length Bruton tyrosine kinase (Btk) from synchrotron X-ray solution scattering

AUTOR(ES)

Márquez, José A.

FONTE

Oxford University Press

RESUMO

Brutons’s tyrosine kinase (Btk) is a non-receptor protein tyrosine kinase (nrPTK) essential for the development of B lymphocytes in humans and mice. Like Src and Abl PTKs, Btk contains a conserved cassette formed by SH3, SH2 and protein kinase domains, but differs from them by the presence of an N-terminal PH domain and the Tec homology region. The domain structure of Btk was analysed using X-ray synchrotron radiation scattering in solution. Low resolution shapes of the full-length protein and several deletion mutants determined ab initio from the scattering data indicated a linear arrangement of domains. This arrangement was further confirmed by rigid body modelling using known high resolution structures of individual domains. The final model of Btk displays an extended conformation with no, or little, inter-domain interactions. In agreement with these results, deletion of non-catalytic domains failed to enhance the activity of Btk. Taken together, our results indicate that, contrary to Src and Abl, Btk might not require an assembled conformation for the regulation of its activity.

Documentos Relacionados

• Crystallization and preliminary X-ray crystallographic analysis of full-length yeast tropomyosin 2 from Saccharomyces cerevisiae
• Fluctuation x-ray scattering from biological particles in frozen solution by using synchrotron radiation.
• Chromatin superstructure: synchrotron radiation X-ray scattering study on solutions and gels.
• Mutações no gene da tirosina quinase de Bruton (Btk) de pacientes brasileiros com agamaglobulinemia ligada ao X (XLA)
• Determination of three-dimensional low-resolution viral structure from solution x-ray scattering data.