Sandbox Reserved 1124: Difference between revisions

'''The SH2 domain'''

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>]]

'''The N-Terminal SH3 domain'''

<scene name='71/719865/Sh3_domain_1/1'>The N-terminal SH3 domain</scene> plays the main role in the interaction with the SOS protein. It binds a proline-rich motif PxxP of the C-Terminal domain of SOS<ref name="a">DOI:10.1038/nsb1294-898</ref> and this binding region in SOS has the shape of a Polyprolin II helix.  

The N-terminal SH3 domain encompasses two three-stranded antiparallel β-sheets, one strand crosses the two sheets. This confers a barrel-like structure upon the domain. The first sheet contains the 3 following strands: S1 (Glu2-Ala5), S2 (Ile24-Lys26) and S6 (Ile53-Met55). The second sheet contains the strands S3 (Val27-Asn29), S4 (Trp36-Leu41) and S5 (Asp45-Ile48). The structure of this SH3 domain is stabilized by a high number of hydrophobic residues, which form the centre of the protein.<ref name="a"/>

'''The C-terminal SH3 domain'''

<scene name='71/719865/C-terminal_sh3_domains/1'>The C-terminal SH3 domain</scene> improves the overall stability of the Grb2-SOS complex.<ref >DOI: http://dx.doi.org/10.1016/1074-5521(95)90080-2</ref>

Moreover, this C-Terminal domain specifically binds to proteins with a P-X-I/L/V-D/N-R-X-X-K-P motif such as Gab1.<ref>DOI:10.1016/S0960-9822(02)01038-2</ref>