7KK7

crystal structure of ligand-free PLEKHA7 PH domain

7KK7 の概要

• エントリーDOI: 10.2210/pdb7kk7/pdb
• 関連するPDBエントリー: 7KJO 7KJZ
• 分子名称: Pleckstrin homology domain-containing family A member 7, GLYCEROL, 1,2-ETHANEDIOL, ... (4 entities in total)
• 機能のキーワード: plekha7, ph domain, pleckstrin homology domain, pip, inositol-phosphate, cell adhesion
• 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: 29183.04

構造登録者

Marassi, F.M.,Aleshin, A.E.,Liddington, R.C. (登録日: 2020-10-27, 公開日: 2021-04-07, 最終更新日: 2023-10-18)

主引用文献

Aleshin, A.E.,Yao, Y.,Iftikhar, A.,Bobkov, A.A.,Yu, J.,Cadwell, G.,Klein, M.G.,Dong, C.,Bankston, L.A.,Liddington, R.C.,Im, W.,Powis, G.,Marassi, F.M.
Structural basis for the association of PLEKHA7 with membrane-embedded phosphatidylinositol lipids.
Structure, 29:1029-, 2021

PubMed Abstract: PLEKHA7 (pleckstrin homology domain containing family A member 7) plays key roles in intracellular signaling, cytoskeletal organization, and cell adhesion, and is associated with multiple human cancers. The interactions of its pleckstrin homology (PH) domain with membrane phosphatidyl-inositol-phosphate (PIP) lipids are critical for proper cellular localization and function, but little is known about how PLEKHA7 and other PH domains interact with membrane-embedded PIPs. Here we describe the structural basis for recognition of membrane-bound PIPs by PLEHA7. Using X-ray crystallography, nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, we show that the interaction of PLEKHA7 with PIPs is multivalent, distinct from a discrete one-to-one interaction, and induces PIP clustering. Our findings reveal a central role of the membrane assembly in mediating protein-PIP association and provide a roadmap for understanding how the PH domain contributes to the signaling, adhesion, and nanoclustering functions of PLEKHA7.

PubMed: 33878292
DOI: 10.1016/j.str.2021.03.018

実験手法

X-RAY DIFFRACTION (2.8 Å)