1QQG

CRYSTAL STRUCTURE OF THE PH-PTB TARGETING REGION OF IRS-1

1QQG の概要

• エントリーDOI: 10.2210/pdb1qqg/pdb
• 分子名称: INSULIN RECEPTOR SUBSTRATE 1 (2 entities in total)
• 機能のキーワード: beta-sandwhich, signal transduction
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 58312.04

構造登録者

Dhe-Paganon, S.,Shoelson, S.E. (登録日: 1999-06-04, 公開日: 1999-08-01, 最終更新日: 2024-02-14)

主引用文献

Dhe-Paganon, S.,Ottinger, E.A.,Nolte, R.T.,Eck, M.J.,Shoelson, S.E.
Crystal structure of the pleckstrin homology-phosphotyrosine binding (PH-PTB) targeting region of insulin receptor substrate 1.
Proc.Natl.Acad.Sci.USA, 96:8378-8383, 1999

PubMed Abstract: We have determined the crystal structure at 2.3-A resolution of an amino-terminal segment of human insulin receptor substrate 1 that encompasses its pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains. Both domains adopt the canonical seven-stranded beta-sandwich PH domain fold. The domains are closely associated, with a 720-A(2) contact surface buried between them that appears to be stabilized by ionic, hydrophobic, and hydrogen bonding interactions. The nonconserved 46-residue linker between the domains is disordered. The PTB domain peptide binding site is fully exposed on the molecular surface, as is a large cationic patch at the base of the PH domain that is a likely binding site for the head groups of phosphatidylinositol phosphates. Binding assays confirm that phosphatidylinositol phosphates bind the PH domain, but not the PTB domain. Ligand binding to the PH domain does not alter PTB domain interactions, and vice versa. The structural and accompanying functional data illustrate how the two binding domains might act cooperatively to effectively increase local insulin receptor substrate 1 concentration at the membrane and transiently fix the receptor and substrate, to allow multiple phosphorylation reactions to occur during each union.

PubMed: 10411883
DOI: 10.1073/pnas.96.15.8378

実験手法

X-RAY DIFFRACTION (2.3 Å)