Sandbox Reserved 1124: Difference between revisions
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Grb2 is a small protein of 217 residues with a molecular mass of about 25,206 Da and composed of three remarkable domains : a single SH2 (Src Homology 2) domain (60 to 152 pdb) flanked by two conserved SH3 domains (respectively 1 to 58 and 156 to 215 pdb)<ref name="A">Gagani Athauda, Donald P Bottaro Atlas of Genetics and Cytogenetics in Oncology and Haematology (2007)[http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html]</ref>. It has no catalytic domain. | Grb2 is a small protein of 217 residues with a molecular mass of about 25,206 Da and composed of three remarkable domains : a single SH2 (Src Homology 2) domain (60 to 152 pdb) flanked by two conserved SH3 domains (respectively 1 to 58 and 156 to 215 pdb)<ref name="A">Gagani Athauda, Donald P Bottaro Atlas of Genetics and Cytogenetics in Oncology and Haematology (2007)[http://atlasgeneticsoncology.org/Genes/GRB2ID386ch17q25.html]</ref>. It has no catalytic 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. | 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 two SH3 domains bind proline-rich regions of other proteins and enable the interaction with the Sos protein (guanine nucleotide exchange factor). The N-Terminal SH3 domain plays the main role in this interaction, it binds a proline-rich motif PxxP of the Ct domain of Sos.<ref>DOI:10.1038/nsb1294-898</ref> This binding region in Sos has the shape of a Polyprolin II helix. The Ct SH3 domain improves the overall stability of the Grb2-Sos complex. Moreover,this Ct 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> | The two SH3 domains bind proline-rich regions of other proteins and enable the interaction with the Sos protein (guanine nucleotide exchange factor). The N-Terminal SH3 domain plays the main role in this interaction, it binds a proline-rich motif PxxP of the Ct domain of Sos.<ref name="1">DOI:10.1038/nsb1294-898</ref> This binding region in Sos has the shape of a Polyprolin II helix. The Ct SH3 domain improves the overall stability of the Grb2-Sos complex. Moreover,this Ct 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> | ||
===The SH2 domain=== | ===The SH2 domain=== | ||
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=== The N-Terminal SH3 domain=== | === The N-Terminal SH3 domain=== | ||
<scene name='71/719865/Sh3_domain_1/1'>The N-terminal SH3 domains</scene> encompasse 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> | <scene name='71/719865/Sh3_domain_1/1'>The N-terminal SH3 domains</scene> encompasse 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="1"></ref> | ||
