Intermolecular interactions between the SH3 domain and the proline-rich TH region of Bruton's tyrosine kinase.
The SH3 domain of Bruton's tyrosine kinase (Btk) is preceded by the Tec homology (TH) region containing proline-rich sequences. We have studied a protein fragment containing both the Btk SH3 domain and the proline-rich sequences of the TH region (PRR-SH3). Intermolecular NMR cross-relaxation measurements, gel permeation chromatography profiles, titrations with proline-rich peptides, and (15)N NMR relaxation measurements are all consistent with a monomer-dimer equilibrium with a dissociation constant on the order of 60 microM. The intermolecular interactions do, at least in part, involve proline-rich sequences in the TH region. This behavior of Btk PRR-SH3 may have implications for the functional action of Btk.
Department of Biotechnology, Royal Institute of Technology, Center for Structural Biochemistry, Novum, Sweden.
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H
Hansson
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Okoh
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Smith
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Vihinen
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Härd
D000077329:Agammaglobulinaemia Tyrosine Kinase; D002850:Chromatography, Gel; D004268:DNA-Binding Proteins / Q000737:chemistry; D019281:Dimerization; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D011505:Protein-Tyrosine Kinases / Q000737:chemistry*; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D015398:Signal Transduction / Q000502:physiology; D013997:Time Factors; D018909:src Homology Domains / Q000502:physiology*
D004268:DNA-Binding Proteins; C490412:NR4A3 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D011392:Proline; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human