3TKZ

Structure of the SHP-2 N-SH2 domain in a 1:2 complex with RVIpYFVPLNR peptide

3TKZ の概要

• エントリーDOI: 10.2210/pdb3tkz/pdb
• 関連するPDBエントリー: 3TL0
• 分子名称: Tyrosine-protein phosphatase non-receptor type 11, PROTEIN (RVIpYFVPLNR peptide) (3 entities in total)
• 機能のキーワード: sh2 domain, protein protein interactions, ptr residues, hydrolase-peptide complex, hydrolase/peptide
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q06124
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 15005.79

構造登録者

Zhang, Y.,Zhang, J.,Yuan, C.,Hard, R.L.,Park, I.H.,Li, C.,Bell, C.E.,Pei, D. (登録日: 2011-08-29, 公開日: 2011-10-26, 最終更新日: 2024-10-16)

主引用文献

Zhang, Y.,Zhang, J.,Yuan, C.,Hard, R.L.,Park, I.H.,Li, C.,Bell, C.,Pei, D.
Simultaneous binding of two peptidyl ligands by a SRC homology 2 domain.
Biochemistry, 50:7637-7646, 2011

PubMed Abstract: Src homology 2 (SH2) domains mediate protein-protein interactions by recognizing phosphotyrosine (pY)-containing sequences of target proteins. In all of the SH2 domain-pY peptide interactions described to date, the SH2 domain binds to a single pY peptide. Here, determination of the cocrystal structure of the N-terminal SH2 domain of phosphatase SHP-2 bound to a class IV peptide (VIpYFVP) revealed a noncanonical 1:2 (protein-peptide) complex. The first peptide binds in a canonical manner with its pY side chain inserted in the usual binding pocket, while the second pairs up with the first to form two antiparallel β-strands that extend the central β-sheet of the SH2 domain. This unprecedented binding mode was confirmed in the solution phase by NMR experiments and shown to be adopted by pY peptides derived from cellular proteins. Site-directed mutagenesis and surface plasmon resonance studies revealed that the binding of the first peptide is pY-dependent, but phosphorylation is not required for the second peptide. Our findings suggest a potential new function for the SH2 domain as a molecular clamp to promote dimerization of signaling proteins.

PubMed: 21800896
DOI: 10.1021/bi200439v

実験手法

X-RAY DIFFRACTION (1.8 Å)