6ICH

Grb2 SH2 domain in domain swapped dimer form

6ICH の概要

• エントリーDOI: 10.2210/pdb6ich/pdb
• 分子名称: Growth factor receptor-bound protein 2 (2 entities in total)
• 機能のキーワード: src homology 2 domain, phosphorylated tyrosine, adapter protein, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 10998.40

構造登録者

Hosoe, Y.,Numoto, N.,Inaba, S.,Ogawa, S.,Morii, H.,Abe, R.,Ito, N.,Oda, M. (登録日: 2018-09-06, 公開日: 2019-07-17, 最終更新日: 2023-11-22)

主引用文献

Hosoe, Y.,Numoto, N.,Inaba, S.,Ogawa, S.,Morii, H.,Abe, R.,Ito, N.,Oda, M.
Structural and functional properties of Grb2 SH2 dimer in CD28 binding.
Biophys Physicobio., 16:80-88, 2019

PubMed Abstract: 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°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 Å resolution, which is currently the highest resolution analysis, and another is dimer at 2.00 Å 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.

PubMed: 30923665
DOI: 10.2142/biophysico.16.0_80

実験手法

X-RAY DIFFRACTION (2 Å)