Both proline‐rich sequences in the TH region of Bruton's tyrosine kinase stabilize intermolecular interactions with the SH3 domain

FEBS Letters

Smith, C.I.Edvard²  Hansson, Henrik¹  Härd, Torleif¹ 

[1] Department of Biotechnology, Royal Institute of Technology (KTH), SCFAB, S-106 91 Stockholm, Sweden;Department of Biosciences at Novum, Karolinska Institute, S-141 57 Huddinge, Sweden

关键词: Bruton's tyrosine kinase;    Src homology 3;    Dimerization;    Nuclear magnetic resonance;    Gel permeation chromatography;    Signal transduction;    Btk;    Bruton's tyrosine kinase;    SH3 domain;    Src homology 3 domain;    TH region;    Tec homology region;    PRR–SH3;    N-terminally extended Btk SH3 domain containing the proline-rich sequences of the TH region;    NMR;    nuclear magnetic resonance;    GPC;    gel permeation chromatography;    GST;    glutathione S-transferase;   

DOI  :  10.1016/S0014-5793(01)03018-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The Tec homology (TH) region located N-terminal to the Src homology 3 (SH3) domain of Bruton's tyrosine kinase (Btk) contains two proline-rich SH3-binding sequences (PRRs). We have previously demonstrated that the TH region acts to stabilize intermolecular interactions in N-terminally extended SH3 (PRR–SH3) fragments. Here, we analyze six PRR–SH3 fragments with different proline-to-alanine substitutions in the two PRRs. Gel permeation chromatography and nuclear magnetic resonance spectroscopy show that both PRRs can stabilize self-association. This observation provides an explanation to why the TH region of Btk makes intermolecular interactions, whereas the corresponding interaction in the related Itk kinase with only one PRR, is intramolecular.

【 授权许可】

Unknown