1awx Citations

Solution structure of the SH3 domain from Bruton's tyrosine kinase.

Biochemistry 37 2912-24 (1998)
Cited: 34 times
EuropePMC logo PMID: 9485443


X-linked agammaglobulinemia (XLA) is a heritable immunodeficiency caused by mutations in the gene coding for Bruton's tyrosine kinase (Btk). Btk belongs to the Tec family of tyrosine kinases. Each member of the family contains five regions and mutations causing XLA have been isolated in all five regions. We have determined the solution structure of the Src homology 3 (SH3) domain of Btk using two- and three-dimensional nuclear magnetic resonance (NMR) spectroscopy on natural abundance and 15N-labeled protein material. The structure determination is complemented by investigation of backbone dynamics based on 15N NMR relaxation. The Btk SH3 forms a well-defined structure and shows the typical SH3 topology of two short antiparallel beta-sheets packed almost perpendicular to each other in a sandwich-like fold. The N- and C-termini are more flexible as are peptide fragments in the RT and n-Src loops. The studied Btk SH3 fragment adopts two slowly interconverting conformations with a relative concentration ratio of 7:1. The overall fold of the minor form is similar to that of the major form, as judged on the basis of observed NOE connectivities and small chemical shift differences. A tryptophan (W251) ring flip is the favored mechanism for interconversion, although other possibilities cannot be excluded. The side chain of Y223, which becomes autophosphorylated upon activation of Btk, is exposed within the potential SH3 ligand binding site. Finally, we compare the present Btk SH3 structure with other SH3 structures.

Articles - 1awx mentioned but not cited (2)

  1. The peroxisomal membrane protein Pex13p shows a novel mode of SH3 interaction. Barnett P, Bottger G, Klein AT, Tabak HF, Distel B. EMBO J. 19 6382-6391 (2000)
  2. The accessory factor Nef links HIV-1 to Tec/Btk kinases in an Src homology 3 domain-dependent manner. Tarafdar S, Poe JA, Smithgall TE. J. Biol. Chem. 289 15718-15728 (2014)

Reviews citing this publication (8)

  1. The role of Bruton's tyrosine kinase in autoimmunity and implications for therapy. Crofford LJ, Nyhoff LE, Sheehan JH, Kendall PL. Expert Rev Clin Immunol 12 763-773 (2016)
  2. TEC family kinases in health and disease--loss-of-function of BTK and ITK and the gain-of-function fusions ITK-SYK and BTK-SYK. Hussain A, Yu L, Faryal R, Mohammad DK, Mohamed AJ, Smith CI. FEBS J. 278 2001-2010 (2011)
  3. The Src, Syk, and Tec family kinases: distinct types of molecular switches. Bradshaw JM. Cell. Signal. 22 1175-1184 (2010)
  4. BTKbase: the mutation database for X-linked agammaglobulinemia. Väliaho J, Smith CI, Vihinen M. Hum. Mutat. 27 1209-1217 (2006)
  5. Bruton's tyrosine kinase: cell biology, sequence conservation, mutation spectrum, siRNA modifications, and expression profiling. Lindvall JM, Blomberg KE, Väliaho J, Vargas L, Heinonen JE, Berglöf A, Mohamed AJ, Nore BF, Vihinen M, Smith CI. Immunol. Rev. 203 200-215 (2005)
  6. Tec family kinases in T lymphocyte development and function. Berg LJ, Finkelstein LD, Lucas JA, Schwartzberg PL. Annu. Rev. Immunol. 23 549-600 (2005)
  7. The Tec family of cytoplasmic tyrosine kinases: mammalian Btk, Bmx, Itk, Tec, Txk and homologs in other species. Smith CI, Islam TC, Mattsson PT, Mohamed AJ, Nore BF, Vihinen M. Bioessays 23 436-446 (2001)
  8. X-linked agammaglobulinemia: lack of mature B lineage cells caused by mutations in the Btk kinase. Smith CI, Bäckesjö CM, Berglöf A, Brandén LJ, Islam T, Mattsson PT, Mohamed AJ, Müller S, Nore B, Vihinen M. Springer Semin. Immunopathol. 19 369-381 (1998)

Articles citing this publication (24)

  1. The role of backbone motions in ligand binding to the c-Src SH3 domain. Wang C, Pawley NH, Nicholson LK. J. Mol. Biol. 313 873-887 (2001)
  2. Mutations of the human BTK gene coding for bruton tyrosine kinase in X-linked agammaglobulinemia. Vihinen M, Kwan SP, Lester T, Ochs HD, Resnick I, Väliaho J, Conley ME, Smith CI. Hum. Mutat. 13 280-285 (1999)
  3. Partial unfolding of diverse SH3 domains on a wide timescale. Wales TE, Engen JR. J. Mol. Biol. 357 1592-1604 (2006)
  4. Conformation of full-length Bruton tyrosine kinase (Btk) from synchrotron X-ray solution scattering. Márquez JA, Smith CI, Petoukhov MV, Lo Surdo P, Mattsson PT, Knekt M, Westlund A, Scheffzek K, Saraste M, Svergun DI. EMBO J. 22 4616-4624 (2003)
  5. Proline isomerization preorganizes the Itk SH2 domain for binding to the Itk SH3 domain. Severin A, Joseph RE, Boyken S, Fulton DB, Andreotti AH. J. Mol. Biol. 387 726-743 (2009)
  6. Effect of pH and salt bridges on structural assembly: molecular structures of the monomer and intertwined dimer of the Eps8 SH3 domain. Kishan KV, Newcomer ME, Rhodes TH, Guilliot SD. Protein Sci. 10 1046-1055 (2001)
  7. Ligand-induced changes in dynamics in the RT loop of the C-terminal SH3 domain of Sem-5 indicate cooperative conformational coupling. Ferreon JC, Hilser VJ. Protein Sci. 12 982-996 (2003)
  8. Intermolecular interactions between the SH3 domain and the proline-rich TH region of Bruton's tyrosine kinase. Hansson H, Okoh MP, Smith CI, Vihinen M, Härd T. FEBS Lett. 489 67-70 (2001)
  9. The response of internal dynamics to hydrophobic core mutations in the SH3 domain from the Fyn tyrosine kinase. Mittermaier A, Kay LE. Protein Sci. 13 1088-1099 (2004)
  10. Competing modes of self-association in the regulatory domains of Bruton's tyrosine kinase: intramolecular contact versus asymmetric homodimerization. Laederach A, Cradic KW, Brazin KN, Zamoon J, Fulton DB, Huang XY, Andreotti AH. Protein Sci. 11 36-45 (2002)
  11. Mechanism and functional significance of Itk autophosphorylation. Joseph RE, Fulton DB, Andreotti AH. J. Mol. Biol. 373 1281-1292 (2007)
  12. Stability and peptide binding specificity of Btk SH2 domain: molecular basis for X-linked agammaglobulinemia. Tzeng SR, Pai MT, Lung FD, Wu CW, Roller PP, Lei B, Wei CJ, Tu SC, Chen SH, Soong WJ, Cheng JW. Protein Sci. 9 2377-2385 (2000)
  13. Conformational snapshots of Tec kinases during signaling. Joseph RE, Andreotti AH. Immunol. Rev. 228 74-92 (2009)
  14. Phosphorylation of Bruton's tyrosine kinase by c-Abl. Bäckesjö CM, Vargas L, Superti-Furga G, Smith CI. Biochem. Biophys. Res. Commun. 299 510-515 (2002)
  15. Backbone dynamics of the human MIA protein studied by (15)N NMR relaxation: implications for extended interactions of SH3 domains. Stoll R, Renner C, Buettner R, Voelter W, Bosserhoff AK, Holak TA. Protein Sci. 12 510-519 (2003)
  16. Regulation of nucleocytoplasmic shuttling of Bruton's tyrosine kinase (Btk) through a novel SH3-dependent interaction with ankyrin repeat domain 54 (ANKRD54). Gustafsson MO, Hussain A, Mohammad DK, Mohamed AJ, Nguyen V, Metalnikov P, Colwill K, Pawson T, Smith CI, Nore BF. Mol. Cell. Biol. 32 2440-2453 (2012)
  17. Interaction between Btk TH and SH3 domain. Okoh MP, Vihinen M. Biopolymers 63 325-334 (2002)
  18. Research Support, Non-U.S. Gov't Identification of novel non-pathogenic mutation in SH3 domain of Btk in an XLA patient. Pérez de Diego R, Bravo J, Allende LM, López-Granados E, Rivera J, Ferreira A, Fontán G, García Rodríguez MC. Mol. Immunol. 45 301-303 (2008)
  19. Both proline-rich sequences in the TH region of Bruton's tyrosine kinase stabilize intermolecular interactions with the SH3 domain. Hansson H, Smith CI, Härd T. FEBS Lett. 508 11-15 (2001)
  20. Murine Itk SH3 domain. Severin A, Fulton DB, Andreotti AH. J. Biomol. NMR 40 285-290 (2008)
  21. Rational design and purification of human Bruton's tyrosine kinase SH3-SH2 protein for structure-function studies. Nera KP, Brockmann E, Vihinen M, Smith CI, Mattsson PT. Protein Expr. Purif. 20 365-371 (2000)
  22. Autoinhibition of Bruton's tyrosine kinase (Btk) and activation by soluble inositol hexakisphosphate. Wang Q, Vogan EM, Nocka LM, Rosen CE, Zorn JA, Harrison SC, Kuriyan J. Elife 4 (2015)
  23. Consequences of two naturally occurring missense mutations in the structure and function of Bruton agammaglobulinemia tyrosine kinase. Vargas-Hernández A, López-Herrera G, Maravillas-Montero JL, Vences-Catalán F, Mogica-Martínez D, Rojo-Domínguez A, Espinosa-Rosales FJ, Santos-Argumedo L. IUBMB Life 64 346-353 (2012)
  24. Dynamics of the Tec-family tyrosine kinase SH3 domains. Roberts JM, Tarafdar S, Joseph RE, Andreotti AH, Smithgall TE, Engen JR, Wales TE. Protein Sci. 25 852-864 (2016)