Intermolecular interactions between the SH3 domain and the proline-rich THregion of Bruton's tyrosine kinase

The SH3 domain of Bruton's tyrosine kinase (Btk) is preceded by the Tec hom ology (TH) region containing proline-rich sequences. We have studied a prot ein fragment containing both the Btk SH3 domain and the proline-rich sequen ces of the TH region (PRR-SH3). Intermolecular NMR cross-relaxation measure ments, gel permeation chromatography profiles, titrations with proline-rich peptides, and N-15 NMR relaxation measurements are all consistent with a m onomer-dimer equilibrium with a dissociation constant on the order of 60 mu M. The intermolecular interactions do, at least in part, involve proline-ri ch sequences in the TH region. This behavior of Btk PRR-SH3 may have implic ations for the functional action of Btk. (C) 2001 Federation of European Bi ochemical Societies. Published by Elsevier Science B.V. All rights reserved .