3I5R

PI3K SH3 domain in complex with a peptide ligand

3I5R の概要

• エントリーDOI: 10.2210/pdb3i5r/pdb
• 関連するPDBエントリー: 3I5S
• 分子名称: Phosphatidylinositol 3-kinase regulatory subunit alpha, Peptide ligand (3 entities in total)
• 機能のキーワード: sh3 domain, peptide complex, alternative splicing, disease mutation, host-virus interaction, phosphoprotein, polymorphism, sh2 domain, ubl conjugation, protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 10780.98

構造登録者

Batra-Safferling, R.,Granzin, J.,Modder, S.,Hoffmann, S.,Willbold, D. (登録日: 2009-07-06, 公開日: 2010-03-02, 最終更新日: 2023-09-06)

主引用文献

Batra-Safferling, R.,Granzin, J.,Modder, S.,Hoffmann, S.,Willbold, D.
Structural studies of the phosphatidylinositol 3-kinase (PI3K) SH3 domain in complex with a peptide ligand: role of the anchor residue in ligand binding.
Biol.Chem., 391:33-42, 2010

PubMed Abstract: Src homology 3 (SH3) domains are mediators of protein-protein interactions. They comprise approximately 60 amino acid residues and are found in many intracellular signaling proteins. Here, we present the crystal structure of the SH3 domain from phosphatidylinositol 3-kinase (PI3K) in complex with the 12-residue proline-rich peptide PD1R (HSKRPLPPLPSL). The crystal structure of the PI3K SH3-PD1R complex at a resolution of 1.7 A reveals type I ligand orientation of the bound peptide with an extended conformation where the central portion forms a left-handed type II polyproline (PPII) helix. The overall structure of the SH3 domain shows minimal changes on ligand binding. In addition, we also attempted crystallization with another peptide ligand (PD1) where the residue at anchor position P(-3) is a tyrosine. The crystals obtained did not contain the PD1 ligand; instead, the ligand binding site is partially occupied by residues Arg18 and Trp55 from the symmetry-related PI3K SH3 molecule. Considering these crystal structures of PI3K SH3 together with published reports, we provide a comparative analysis of protein-ligand interactions that has helped us identify the individual residues which play an important role in defining target specificity.

PubMed: 19919182
DOI: 10.1515/BC.2010.003

実験手法

X-RAY DIFFRACTION (1.7 Å)