3bun Citations

Structural basis for a novel intrapeptidyl H-bond and reverse binding of c-Cbl-TKB domain substrates.

EMBO J. 27 804-16 (2008)
Related entries: 3bux, 3buw, 3bum, 3buo

Cited: 30 times
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The c-Cbl tyrosine kinase binding domain (Cbl-TKB), essentially an 'embedded' SH2 domain, has a critical role in targeting proteins for ubiquitination. To address how this domain can bind to disparate recognition mofits and to determine whether this results in variations in substrate-binding affinity, we compared crystal structures of the Cbl-TKB domain complexed with phosphorylated peptides of Sprouty2, Sprouty4, epidermal growth factor receptor, Syk, and c-Met receptors and validated the binding with point-mutational analyses using full-length proteins. An obligatory, intrapeptidyl H-bond between the phosphotyrosine and the conserved asparagine or adjacent arginine is essential for binding and orients the peptide into a positively charged pocket on c-Cbl. Surprisingly, c-Met bound to Cbl in the reverse direction, which is unprecedented for SH2 domain binding. The necessity of this intrapeptidyl H-bond was confirmed with isothermal titration calorimetry experiments that also showed Sprouty2 to have the highest binding affinity to c-Cbl; this may enable the selective sequestration of c-Cbl from other target proteins.

Reviews citing this publication (10)

  1. Degrons in cancer. Mészáros B, Kumar M, Gibson TJ, Uyar B, Dosztányi Z. Sci Signal 10 (2017)
  2. Design Principles Involving Protein Disorder Facilitate Specific Substrate Selection and Degradation by the Ubiquitin-Proteasome System. Guharoy M, Bhowmick P, Tompa P. J Biol Chem 291 6723-6731 (2016)
  3. The developing story of Sprouty and cancer. Masoumi-Moghaddam S, Amini A, Morris DL. Cancer Metastasis Rev 33 695-720 (2014)
  4. Protein tyrosine kinase regulation by ubiquitination: critical roles of Cbl-family ubiquitin ligases. Mohapatra B, Ahmad G, Nadeau S, Zutshi N, An W, Scheffe S, Dong L, Feng D, Goetz B, Arya P, Bailey TA, Palermo N, Borgstahl GE, Natarajan A, Raja SM, Naramura M, Band V, Band H. Biochim Biophys Acta 1833 122-139 (2013)
  5. Molecular mechanisms of SH2- and PTB-domain-containing proteins in receptor tyrosine kinase signaling. Wagner MJ, Stacey MM, Liu BA, Pawson T. Cold Spring Harb Perspect Biol 5 a008987 (2013)
  6. Cbl-family proteins as regulators of cytoskeleton-dependent phenomena. Lee H, Tsygankov AY. J Cell Physiol 228 2285-2293 (2013)
  7. The language of SH2 domain interactions defines phosphotyrosine-mediated signal transduction. Liu BA, Engelmann BW, Nash PD. FEBS Lett 586 2597-2605 (2012)
  8. Survey of the year 2008: applications of isothermal titration calorimetry. Falconer RJ, Penkova A, Jelesarov I, Collins BM. J Mol Recognit 23 395-413 (2010)
  9. Syk and pTyr'd: Signaling through the B cell antigen receptor. Geahlen RL. Biochim Biophys Acta 1793 1115-1127 (2009)
  10. Intermolecular interactions of Sprouty proteins and their implications in development and disease. Edwin F, Anderson K, Ying C, Patel TB. Mol Pharmacol 76 679-691 (2009)

Articles citing this publication (20)

  1. Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl. Dou H, Buetow L, Hock A, Sibbet GJ, Vousden KH, Huang DT. Nat Struct Mol Biol 19 184-192 (2012)
  2. Molecular mechanisms of ubiquitin-dependent membrane traffic. Hurley JH, Stenmark H. Annu Rev Biophys 40 119-142 (2011)
  3. Essentiality of a non-RING element in priming donor ubiquitin for catalysis by a monomeric E3. Dou H, Buetow L, Sibbet GJ, Cameron K, Huang DT. Nat Struct Mol Biol 20 982-986 (2013)
  4. SLiMPrints: conservation-based discovery of functional motif fingerprints in intrinsically disordered protein regions. Davey NE, Cowan JL, Shields DC, Gibson TJ, Coldwell MJ, Edwards RJ. Nucleic Acids Res 40 10628-10641 (2012)
  5. Structure of a novel phosphotyrosine-binding domain in Hakai that targets E-cadherin. Mukherjee M, Chow SY, Yusoff P, Seetharaman J, Ng C, Sinniah S, Koh XW, Asgar NF, Li D, Yim D, Jackson RA, Yew J, Qian J, Iyu A, Lim YP, Zhou X, Sze SK, Guy GR, Sivaraman J. EMBO J 31 1308-1319 (2012)
  6. Tripartite degrons confer diversity and specificity on regulated protein degradation in the ubiquitin-proteasome system. Guharoy M, Bhowmick P, Sallam M, Tompa P. Nat Commun 7 10239 (2016)
  7. HECT domain-containing E3 ubiquitin ligase Nedd4 interacts with and ubiquitinates Sprouty2. Edwin F, Anderson K, Patel TB. J Biol Chem 285 255-264 (2010)
  8. c-Cbl tyrosine kinase-binding domain mutant G306E abolishes the interaction of c-Cbl with CD38 and fails to promote retinoic acid-induced cell differentiation and G0 arrest. Shen M, Yen A. J Biol Chem 284 25664-25677 (2009)
  9. High-throughput fluorescence polarization assay to identify inhibitors of Cbl(TKB)-protein tyrosine kinase interactions. Kumar EA, Charvet CD, Lokesh GL, Natarajan A. Anal Biochem 411 254-260 (2011)
  10. Two structural motifs within canonical EF-hand calcium-binding domains identify five different classes of calcium buffers and sensors. Denessiouk K, Permyakov S, Denesyuk A, Permyakov E, Johnson MS. PLoS One 9 e109287 (2014)
  11. Phosphorylation of the MET receptor on juxtamembrane tyrosine residue 1001 inhibits its caspase-dependent cleavage. Deheuninck J, Goormachtigh G, Foveau B, Ji Z, Leroy C, Ancot F, Villeret V, Tulasne D, Fafeur V. Cell Signal 21 1455-1463 (2009)
  12. Additional serine/threonine phosphorylation reduces binding affinity but preserves interface topography of substrate proteins to the c-Cbl TKB domain. Sun Q, Jackson RA, Ng C, Guy GR, Sivaraman J. PLoS One 5 e12819 (2010)
  13. Peptide truncation leads to a twist and an unusual increase in affinity for casitas B-lineage lymphoma tyrosine kinase binding domain. Kumar EA, Yuan Z, Palermo NY, Dong L, Ahmad G, Lokesh GL, Kolar C, Kizhake S, Borgstahl GE, Band H, Natarajan A. J Med Chem 55 3583-3587 (2012)
  14. The paradox of conformational constraint in the design of Cbl(TKB)-binding peptides. Kumar EA, Chen Q, Kizhake S, Kolar C, Kang M, Chang CE, Borgstahl GE, Natarajan A. Sci Rep 3 1639 (2013)
  15. An adjacent arginine, and the phosphorylated tyrosine in the c-Met receptor target sequence, dictates the orientation of c-Cbl binding. Sun Q, Ng C, Guy GR, Sivaraman J. FEBS Lett 585 281-285 (2011)
  16. Structural determinants of nuclear export signal orientation in binding to exportin CRM1. Fung HY, Fu SC, Brautigam CA, Chook YM. Elife 4 (2015)
  17. Structural flexibility regulates phosphopeptide-binding activity of the tyrosine kinase binding domain of Cbl-c. Takeshita K, Tezuka T, Isozaki Y, Yamashita E, Suzuki M, Kim M, Yamanashi Y, Yamamoto T, Nakagawa A. J Biochem 152 487-495 (2012)
  18. Structural basis for the indispensable role of a unique zinc finger motif in LNX2 ubiquitination. Nayak D, Sivaraman J. Oncotarget 6 34342-34357 (2015)
  19. The Insect Peptide CopA3 Increases Colonic Epithelial Cell Proliferation and Mucosal Barrier Function to Prevent Inflammatory Responses in the Gut. Kim DH, Hwang JS, Lee IH, Nam ST, Hong J, Zhang P, Lu LF, Lee J, Seok H, Pothoulakis C, Lamont JT, Kim H. J Biol Chem 291 3209-3223 (2016)
  20. Casitas B-lineage lymphoma linker helix mutations found in myeloproliferative neoplasms affect conformation. Buetow L, Tria G, Ahmed SF, Hock A, Dou H, Sibbet GJ, Svergun DI, Huang DT. BMC Biol 14 76 (2016)