期刊
STRUCTURE
卷 29, 期 9, 页码 1029-+出版社
CELL PRESS
DOI: 10.1016/j.str.2021.03.018
关键词
-
资金
- National Institutes of Health [GM118186, CA179087, CA160398, CA030199]
- National Science Foundation [MCB1810695]
This study elucidates the structural basis for PLEKHA7 recognition of membrane-bound PIPs, showing that the interaction is multivalent and induces PIP clustering. The findings reveal the central role of membrane assembly in mediating protein-PIP association and provide insights into the function of the PH domain in PLEKHA7 signaling, adhesion, and nanoclustering.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据