title: Both proline-rich sequences in the TH region of Bruton's tyrosine kinase stabilize intermolecular interactions with the SH3 domain.
abstract: 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.
authors.affiliation: Department of Biotechnology, Royal Institute of Technology (KTH), SCFAB, S-106 91 Stockholm, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Hansson
authors.forename: C I
authors.initials: CI
authors.lastname: Smith
authors.forename: T
authors.initials: T
authors.lastname: Härd
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D002850:Chromatography, Gel; D006801:Humans; D016297:Mutagenesis, Site-Directed; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human