Growth factor receptor-bound protein

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<StructureSection load='1tze' size='350' side='right' caption='Structure of human Grb2 SH2 domain (pink) complex with phosphotyrosyl heptapeptide (gold) (PDB entry [[1tze]])' scene=''>
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<StructureSection load='' size='350' side='right' caption='Structure of human Grb2 SH2 domain (green) complex with phosphotyrosyl polypeptide (magenta) (PDB entry [[1bmb]])' scene='51/516448/Cv/1'>
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== Function ==
'''Growth factor receptor-bound proteins''' (GRB) are adaptor proteins. GRBs contain SH2, Ras-associated (RA) and pleckstrin homology (PH) domains. <br />
'''Growth factor receptor-bound proteins''' (GRB) are adaptor proteins. GRBs contain SH2, Ras-associated (RA) and pleckstrin homology (PH) domains. <br />
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* '''GRB2''' links the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases. GRB2 contains an SH2 domain which binds tyrosine phosphorylated sequences and 2 SH3 domains which direct complex formation of proline-rich sequences. GRB2 is involved in signal transduction.<br />
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* '''GRB2''' links the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases. GRB2 contains an SH2 domain which binds tyrosine phosphorylated sequences and 2 SH3 domains which direct complex formation of proline-rich sequences. GRB2 is involved in signal transduction<ref>PMID:1322798</ref>.<br />
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* '''GRB7''' interacts with EGFR and ephrin receptors and plays a role in itegrin signalling pathway.<br />
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* '''GRB7''' interacts with EGFR and ephrin receptors and plays a role in itegrin signalling pathway<ref>PMID:19717535</ref>.<br />
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* '''GRB10''' interacts with insulin receptor and insulin-like growth factor receptors. For additional details on GRB10 see [[Grb10 SH2 Domain]].<br />
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* '''GRB10''' and '''GRB14''' interact with insulin receptor and insulin-like growth factor receptors<ref>PMID:12783867</ref>. For additional details on GRB10 see [[Grb10 SH2 Domain]].<br />
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</StructureSection>
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==3D structures of Grb==
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== Structural highlights ==
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Human GRB2 residue <scene name='51/516448/Cv/5'>Trp121 forces the phosphotyrosyl containing ligand</scene> into a turn conformation. Water molecules are shown as red spheres. <scene name='51/516448/Cv/6'>Phosphotyrosine binding</scene> <ref>PMID:10090780</ref>.
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Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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==3D structures of growth factor receptor-bound proteins==
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{{#tree:id=OrganizedByTopic|openlevels=0|
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[[Growth factor receptor-bound proteins 3D structures]]
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*GRB2
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</StructureSection>
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**[[1gri]], [[2h46]] – hGRB2 – human <br />
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*''GRB2 C terminal SH3 domain''
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**[[1gfc]], [[1gfd]] – hGRB2 C terminal SH3 domain - NMR<br />
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**[[2vvk]], [[2vwf]], [[2w0z]] – hGRB2 C terminal SH3 domain <br />
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**[[1io6]] – hGRB2 C terminal SH3 domain + ligand peptide - NMR<br />
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**[[1gcq]] – hGRB2 C terminal SH3 domain + VAV proto-oncogene SH3 domain<br />
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*''GRB2 N terminal SH3 domain''
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**[[1gbr]], [[1gbq]], [[2gbq]], [[3gbq]], [[4gbq]] – mGRB2 N terminal SH3 domain + Sos-A peptide – mouse - NMR<br />
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**[[1aze]] – mGRB2 N terminal SH3 domain + Sos-A peptide - NMR<br />
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*''GRB2 SH2 domain''
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**[[1jyu]] – hGRB2 SH2 domain <br />
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**[[1ghu]] – hGRB2 SH2 domain (mutant) - NMR<br />
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**[[1fhs]] – hGRB2 SH2 domain - NMR<br />
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**[[1x0n]] – hGRB2 SH2 domain + inhibitor - NMR<br />
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**[[2huw]] – hGRB2 SH2 domain + cyclopropane derivative<br />
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**[[1cj1]] – hGRB2 SH2 domain + phosphor-Tyr derivative<br />
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**[[2aoa]], [[2aob]] – hGRB2 SH2 domain + peptide mimetic<br />
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**[[1tze]], [[1bmb]], [[1bm2]], [[1zfp]], [[1fyr]], [[1jyq]], [[1jyr]], [[2h5k]], [[3c7i]], [[3imd]], [[3imj]], [[3in7]], [[3in8]], [[3kfj]], [[3n8m]], [[3n7y]], [[3n84]], [[3mxc]], [[3mxy]], [[3ov1]], [[3ove]], [[3s8l]], [[3s8n]], [[3s8o]], [[1zfp]] – hGRB2 SH2 domain + phosphor-Tyr peptide<br />
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**[[1qg1]] – hGRB2 SH2 domain + phosphor-Tyr peptide - NMR<br />
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**[[3wa4]] - hGRB2 SH2 domain + CD28 peptide <br />
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*GRB4
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**[[4e6r]] – hGRB4 C terminal SH3 domain <br />
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*GRB7
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**[[2qms]] – hGRB7 SH2 domain <br />
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**[[1mw4]], [[2l4k]] – hGRB7 SH2 domain + phosphor-Tyr peptide - NMR<br />
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**[[3pqz]] – hGRB7 SH2 domain + cyclic peptide <br />
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**[[1wgr]] – hGRB7 RA domain - NMR<br />
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*GRB10
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**[[1nrv]] – hGRB10 SH2 domain <br />
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**[[3m7f]] – hGRB10 SH2 domain + NEDD4 C2 domain<br />
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**[[3hk0]] – hGRB10 RA and PH domains <br />
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*GRB14
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**[[2aug]] – hGRB14 SH2 domain <br />
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== References ==
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**[[2auh]] – hGRB14 BPS domain + insulin receptor kinase domain<br />
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<references/>
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**[[4k81]] – hGRB14 RA and PH domains + GTPase Hras<br />
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}}
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[[Category:Topic Page]]
[[Category:Topic Page]]

Current revision

Structure of human Grb2 SH2 domain (green) complex with phosphotyrosyl polypeptide (magenta) (PDB entry 1bmb)

Drag the structure with the mouse to rotate

References

  1. ↑ Lowenstein EJ, Daly RJ, Batzer AG, Li W, Margolis B, Lammers R, Ullrich A, Skolnik EY, Bar-Sagi D, Schlessinger J. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992 Aug 7;70(3):431-42. PMID:1322798
  2. ↑ Nadler Y, Gonzalez AM, Camp RL, Rimm DL, Kluger HM, Kluger Y. Growth factor receptor-bound protein-7 (Grb7) as a prognostic marker and therapeutic target in breast cancer. Ann Oncol. 2010 Mar;21(3):466-73. doi: 10.1093/annonc/mdp346. Epub 2009 Aug 28. PMID:19717535 doi:http://dx.doi.org/10.1093/annonc/mdp346
  3. ↑ Deng Y, Bhattacharya S, Swamy OR, Tandon R, Wang Y, Janda R, Riedel H. Growth factor receptor-binding protein 10 (Grb10) as a partner of phosphatidylinositol 3-kinase in metabolic insulin action. J Biol Chem. 2003 Oct 10;278(41):39311-22. Epub 2003 Jun 3. PMID:12783867 doi:http://dx.doi.org/10.1074/jbc.M304599200
  4. ↑ Ettmayer P, France D, Gounarides J, Jarosinski M, Martin MS, Rondeau JM, Sabio M, Topiol S, Weidmann B, Zurini M, Bair KW. Structural and conformational requirements for high-affinity binding to the SH2 domain of Grb2(1). J Med Chem. 1999 Mar 25;42(6):971-80. PMID:10090780 doi:10.1021/jm9811007

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