Sandbox Reserved 1124: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 30: | Line 30: | ||
This domain is very essential to the function of Grb2. In fact, <scene name='71/719865/Sh2domains/1'>the SH2 domain</scene> 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.<ref name="polyprolin"/> | This domain is very essential to the function of Grb2. In fact, <scene name='71/719865/Sh2domains/1'>the SH2 domain</scene> 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.<ref name="polyprolin"/> | ||
The central SH2 domain binds growth factor receptors (EGFR or PDGFR) or scaffold proteins. | The central SH2 domain binds growth factor receptors (EGFR or PDGFR) or scaffold proteins. SH2 interacts preferentially with a tyrosine phosphorylated sequence with the following motif: pY-x-N-x (x is a hydrophobic residue).<ref > DOI:10.1371/journal.pone.0074482</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.<ref name="A"/> | ||
The SH2 domain 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 SH2 domain 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>]] | ||
| Line 57: | Line 57: | ||
The determination of the crystallographic structure enabled the observation of the junction between the SH3 and SH2 domains. It allows the two adjacent faces of the SH3 domains to be closer. This association is strenghtened by Van der Waals | The determination of the crystallographic structure enabled the observation of the junction between the SH3 and SH2 domains. It allows the two adjacent faces of the SH3 domains to be closer. This association is strenghtened by Van der Waals interactions. Nevertheless, the proline-rich peptides can still bind to SH3 domains.<ref >PMID: 7716522</ref> And when the SH2 domain of Grb2 binds to a receptor, the ability of the SH3 domains to interact with Sos motifs does not change. <ref> The Biochemistry of Cell Signalling, Ernst J. M. Helmreich, 2001, p.52 [https://global.oup.com/academic/product/the-biochemistry-of-cell-signalling-9780198508205?cc=fr&lang=en&]</ref> | ||
== Functions and interactions with substrates == | == Functions and interactions with substrates == | ||
