Sandbox Reserved 1124: Difference between revisions
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'''The SH2 domain''' | '''The SH2 domain''' | ||
This domain is very essential for the function of Grb2. In fact, the SH2 domain of Grb2 enables the interaction with receptors, scaffold proteins, tyrosine kinases but also with other adaptor proteins. Indeed, Shc is an intermediate between some receptors and Grb2. | |||
The central SH2 domain binds growth factor receptors (EGFR or PDGFR) or scaffold proteins. It interacts preferentially with a tyrosine phosphorylated sequence with the following motif: pY-X-N-X (X is a hydrophobic residue).<ref > Wikipedia Grb2 [https://en.wikipedia.org/wiki/GRB2]</ref>. Other non-receptor tyrosine kinases have also this motif and interact with Grb2 SH2 domain, such as BCR-Abl, focal adhesion kinase, insulin receptor substrate 1 and PTPN11. | The central SH2 domain binds growth factor receptors (EGFR or PDGFR) or scaffold proteins. It interacts preferentially with a tyrosine phosphorylated sequence with the following motif: pY-X-N-X (X is a hydrophobic residue).<ref > Wikipedia Grb2 [https://en.wikipedia.org/wiki/GRB2]</ref>. Other non-receptor tyrosine kinases have also this motif and interact with Grb2 SH2 domain, such as BCR-Abl, focal adhesion kinase, insulin receptor substrate 1 and PTPN11. | ||
<scene name='71/719865/Sh2domains/1'>The SH2 domain</scene> encompasses 8 beta strands (<scene name='71/719865/Beta_strand_61-64/1'>61 to 64</scene> ; <scene name='71/719865/Beta_strand_82-87/1'>82 to 87</scene> ; <scene name='71/719865/Beta_strand_95-101/1'>95 to 101</scene> ; <scene name='71/719865/Beta_strand_104-112/1'>104 to 112</scene> ; <scene name='71/719865/Beta_strand_114-116/1'>114 to 116</scene> ; <scene name='71/719865/Beta_strand_118-122/1'>118 to 122</scene> ; <scene name='71/719865/Beta_strand_124-127/1'>124 to 127</scene> ; <scene name='71/719865/Beta_strand_149-152/2'>149 to 152</scene>) and 2 alpha helices (<scene name='71/719865/Alpha_helix_67-75/1'>67 to 75</scene> and <scene name='71/719865/Alpha_helix_128-134/1'>128 to 134</scene>)<ref> [http://www.uniprot.org/uniprot/P62993 UniProtKB P62993 Human]</ref>. The βB, βC and βD strands compose a three-stranded antiparallel β-sheet and the 2 α-helices are positioned on both sides. Moreover, the short parallel βA and βG strands extend the central β-sheet. There are also βD', βE and βF strands which are smaller β-sheet-like structure. <ref>DOI:10.1007/s10858-008-9272-0</ref> [[Image:Sequence_of_the_SH2_domain_of_Grb2.PNG | thumb | upright=3 | Sequence of the SH2 domain (60 to 152 amino acids) of Grb2 <ref name="Kousik">Kousik Kundu In Silico Prediction of Modular Domain-Peptide Interactions (2015) [https://scholar.google.com/citations?view_op=view_citation&hl=en&user=0iOlQDAAAAAJ&citation_for_view=0iOlQDAAAAAJ:qUcmZB5y_30C]</ref>]] | <scene name='71/719865/Sh2domains/1'>The SH2 domain</scene> encompasses 8 beta strands (<scene name='71/719865/Beta_strand_61-64/1'>61 to 64</scene> ; <scene name='71/719865/Beta_strand_82-87/1'>82 to 87</scene> ; <scene name='71/719865/Beta_strand_95-101/1'>95 to 101</scene> ; <scene name='71/719865/Beta_strand_104-112/1'>104 to 112</scene> ; <scene name='71/719865/Beta_strand_114-116/1'>114 to 116</scene> ; <scene name='71/719865/Beta_strand_118-122/1'>118 to 122</scene> ; <scene name='71/719865/Beta_strand_124-127/1'>124 to 127</scene> ; <scene name='71/719865/Beta_strand_149-152/2'>149 to 152</scene>) and 2 alpha helices (<scene name='71/719865/Alpha_helix_67-75/1'>67 to 75</scene> and <scene name='71/719865/Alpha_helix_128-134/1'>128 to 134</scene>)<ref> [http://www.uniprot.org/uniprot/P62993 UniProtKB P62993 Human]</ref>. The βB, βC and βD strands compose a three-stranded antiparallel β-sheet and the 2 α-helices are positioned on both sides. Moreover, the short parallel βA and βG strands extend the central β-sheet. There are also βD', βE and βF strands which are smaller β-sheet-like structure. <ref>DOI:10.1007/s10858-008-9272-0</ref> [[Image:Sequence_of_the_SH2_domain_of_Grb2.PNG | thumb | upright=3 | Sequence of the SH2 domain (60 to 152 amino acids) of Grb2 <ref name="Kousik">Kousik Kundu In Silico Prediction of Modular Domain-Peptide Interactions (2015) [https://scholar.google.com/citations?view_op=view_citation&hl=en&user=0iOlQDAAAAAJ&citation_for_view=0iOlQDAAAAAJ:qUcmZB5y_30C]</ref>]] | ||
The amino acid in red are residues which are responsible for forming the phosphopeptide binding pocket. In green, these are residues which can bind to the negatively charged phosphorylated tyrosine | The amino acid in red are residues which are responsible for forming the phosphopeptide binding pocket. In green, these are residues which can bind to the negatively charged phosphorylated tyrosine residues of the peptide. This domain is very essential for the function of Grb2. | ||
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== '''Disease''' == | == '''Disease''' == | ||
The phosphorylation of the 160 tyrosine on Grb2 has been observed in many human cancers such as prostate, colon or breast cancers. The switch between the dimeric and monomeric conformations | The phosphorylation of the 160 tyrosine on Grb2 has been observed in many human cancers such as prostate, colon or breast cancers. The switch between the dimeric and monomeric conformations regulates the cancer progression. | ||
Several mutations in the SH2 domains can cause human diseases. For example, it can have a suppression of phosphotyrosine dependent interactions due to a mutation of the arginin residue at position 5 of the βB strand in the SH2 domain.<ref name="Kousik"/> | |||
</StructureSection> | </StructureSection> | ||
