Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix - PubMed

Affiliations

• PMID: 15100220
• DOI: 10.1074/jbc.M402745200

Free article

Mona/Gads SH3C binding to hematopoietic progenitor kinase 1 (HPK1) combines an atypical SH3 binding motif, R/KXXK, with a classical PXXP motif embedded in a polyproline type II (PPII) helix

Marc Lewitzky et al. J Biol Chem. 2004.

Free article

Abstract

Hematopoietic progenitor kinase 1 (HPK1) is implicated in signaling downstream of the T cell receptor. Its non-catalytic, C-terminal half contains several prolinerich motifs, which have been shown to interact with different SH3 domain-containing adaptor proteins in vitro. One of these, Mona/Gads, was also shown to bind HPK1 in mouse T cells in vivo. The region of HPK1 that binds to the Mona/Gads C-terminal SH3 domain has been mapped and shows only very limited similarity to a recently identified high affinity binding motif in SLP-76, another T-cell adaptor. Using isothermal titration calorimetry and x-ray crystallography, the binding of the HPK1 motif to Mona/Gads SH3C has now been characterized in molecular detail. The results indicate that although charge interactions through an RXXK motif are essential for complex formation, a PXXP motif in HPK1 strongly complements binding. This unexpected binding mode therefore differs considerably from the previously described interaction of Mona/Gads SH3C with SLP-76. The crystal structure of the complex highlights the great versatility of SH3 domains, which allows interactions with very different proteins. This currently limits our ability to categorize SH3 binding properties by simple rules.

Similar articles

• Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76.

  Harkiolaki M, Lewitzky M, Gilbert RJ, Jones EY, Bourette RP, Mouchiroud G, Sondermann H, Moarefi I, Feller SM. Harkiolaki M, et al. EMBO J. 2003 Jun 2;22(11):2571-82. doi: 10.1093/emboj/cdg258. EMBO J. 2003. PMID: 12773374 Free PMC article.

• The adaptor protein Gads (Grb2-related adaptor downstream of Shc) is implicated in coupling hemopoietic progenitor kinase-1 to the activated TCR.

  Liu SK, Smith CA, Arnold R, Kiefer F, McGlade CJ. Liu SK, et al. J Immunol. 2000 Aug 1;165(3):1417-26. doi: 10.4049/jimmunol.165.3.1417. J Immunol. 2000. PMID: 10903746

• A high-affinity Arg-X-X-Lys SH3 binding motif confers specificity for the interaction between Gads and SLP-76 in T cell signaling.

  Berry DM, Nash P, Liu SK, Pawson T, McGlade CJ. Berry DM, et al. Curr Biol. 2002 Aug 6;12(15):1336-41. doi: 10.1016/s0960-9822(02)01038-2. Curr Biol. 2002. PMID: 12176364

• Promiscuous binding nature of SH3 domains to their target proteins.

  Agrawal V, Kishan KV. Agrawal V, et al. Protein Pept Lett. 2002 Jun;9(3):185-93. doi: 10.2174/0929866023408760. Protein Pept Lett. 2002. PMID: 12144515 Review.

• Functional interactions of HPK1 with adaptor proteins.

  Boomer JS, Tan TH. Boomer JS, et al. J Cell Biochem. 2005 May 1;95(1):34-44. doi: 10.1002/jcb.20401. J Cell Biochem. 2005. PMID: 15770651 Review.

Cited by

• Evolution of domain-peptide interactions to coadapt specificity and affinity to functional diversity.

  Kelil A, Levy ED, Michnick SW. Kelil A, et al. Proc Natl Acad Sci U S A. 2016 Jul 5;113(27):E3862-71. doi: 10.1073/pnas.1518469113. Epub 2016 Jun 17. Proc Natl Acad Sci U S A. 2016. PMID: 27317745 Free PMC article.

• Expression, refolding and crystallizations of the Grb2-like (GADS) C-terminal SH3 domain complexed with a SLP-76 motif peptide.

  Faravelli A, Dimasi N. Faravelli A, et al. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006 Jan 1;62(Pt 1):52-5. doi: 10.1107/S1744309105041023. Epub 2005 Dec 16. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2006. PMID: 16511262 Free PMC article.

• Structural features of the full-length adaptor protein GADS in solution determined using small-angle X-ray scattering.

  Moran O, Roessle MW, Mariuzza RA, Dimasi N. Moran O, et al. Biophys J. 2008 Mar 1;94(5):1766-72. doi: 10.1529/biophysj.107.116590. Epub 2007 Nov 9. Biophys J. 2008. PMID: 17993503 Free PMC article.

• Grb2 carboxyl-terminal SH3 domain can bivalently associate with two ligands, in an SH3 dependent manner.

  Arya R, Dangi RS, Makwana PK, Kumar A, Upadhyay SK, Sundd M. Arya R, et al. Sci Rep. 2017 Apr 28;7(1):1284. doi: 10.1038/s41598-017-01364-5. Sci Rep. 2017. PMID: 28455498 Free PMC article.

• Efficient T-cell receptor signaling requires a high-affinity interaction between the Gads C-SH3 domain and the SLP-76 RxxK motif.

  Seet BT, Berry DM, Maltzman JS, Shabason J, Raina M, Koretzky GA, McGlade CJ, Pawson T. Seet BT, et al. EMBO J. 2007 Feb 7;26(3):678-89. doi: 10.1038/sj.emboj.7601535. Epub 2007 Jan 18. EMBO J. 2007. PMID: 17235283 Free PMC article.

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Elsevier Science

• Other Literature Sources

  • The Lens - Patent Citations Database

• Molecular Biology Databases

  • BioCyc
  • Gene Ontology
  • GlyGen glycoinformatics resource
  • Mouse Genome Informatics (MGI)