6ich | pdb_00006ich

Grb2 SH2 domain in domain swapped dimer form

spinqualitylabelsall models 6ich, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ich is a 1 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [GRB2_HUMAN] Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death. Publication Abstract from PubMed Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein that plays a critical role in cellular signal transduction. It contains a central Src homology 2 (SH2) domain flanked by two Src homology 3 (SH3) domains. Binding of Grb2 SH2 to the cytoplasmic region of CD28, phosphorylated Tyr (pY) containing the peptide motif pY-X-N-X, is required for costimulatory signaling in T cells. In this study, we purified the dimer and monomer forms of Grb2 SH2, respectively, and analyzed their structural and functional properties. Size exclusion chromatography analysis showed that both dimer and monomer exist as stable states. Thermal stability analysis using circular dichroism showed that the dimer mostly dissociates into the monomer around 50 degrees C. CD28 binding experiments showed that the affinity of the dimer to the phosphopeptide was about three fold higher than that of the monomer, possibly due to the avidity effect. The present crystal structure analysis of Grb2 SH2 showed two forms; one is monomer at 1.15 A resolution, which is currently the highest resolution analysis, and another is dimer at 2.00 A resolution. In the dimer structure, the C-terminal region, comprising residues 123-152, was extended towards the adjacent molecule, in which Trp121 was the hinge residue. The stable dimer purified using size exclusion chromatography would be due to the C-terminal helix "swapping". In cases where a mutation caused Trp121 to be replaced by Ser in Grb2 SH2, this protein still formed dimers, but lost the ability to bind CD28. Structural and functional properties of Grb2 SH2 dimer in CD28 binding.,Hosoe Y, Numoto N, Inaba S, Ogawa S, Morii H, Abe R, Ito N, Oda M Biophys Physicobiol. 2019 Feb 22;16:80-88. doi: 10.2142/biophysico.16.0_80., eCollection 2019. PMID:30923665 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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