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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=''> | | <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'> |
| [[Image:1tze.png|left|200px|thumb|Crystal structure of human Grb2 SH2 domain (pink) complex with phosphotyrosyl heptapeptide (gold) [[1tze]]]]
| | == Function == |
| | | '''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<ref>PMID:1322798</ref>.<br /> |
| '''Growth factor receptor-bound proteins''' (GRB) are adaptor proteins. '''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. '''GRB7''' interacts with EGFR and ephrin receptors and plays a role in itegrin signalling pathway. '''GRB10''' interacts with insulin receptor and insulin-like growth factor receptors. GRBs contain SH2, Ras-associated (RA) and pleckstrin homology (PH) domains. For additional details on GRB10 see [[Grb10 SH2 Domain]]. | | * '''GRB7''' interacts with EGFR and ephrin receptors and plays a role in itegrin signalling pathway<ref>PMID:19717535</ref>.<br /> |
| | | * '''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 /> |
| ==3D structures of Grb==
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| Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
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| ===GRB2===
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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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| [[2auh]] – hGRB14 BPS domain + insulin receptor kinase domain<br />
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| [[4k81]] – hGRB14 RA and PH domains + GTPase Hras<br />
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| | == Structural highlights == |
| | 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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| | ==3D structures of growth factor receptor-bound proteins== |
| | [[Growth factor receptor-bound proteins 3D structures]] |
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| | </StructureSection> |
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| | == References == |
| | <references/> |
| [[Category:Topic Page]] | | [[Category:Topic Page]] |