4K17

Crystal Structure of mouse CARMIL residues 1-668

4K17 の概要

• エントリーDOI: 10.2210/pdb4k17/pdb
• 分子名称: Leucine-rich repeat-containing protein 16A, salicylamide, CHLORIDE ION, ... (4 entities in total)
• 機能のキーワード: ph domain, lrr domain, lipid binding, protein-protein interaction, phosphatidylserine, phosphatidylinositol, phosphatidylinositol-5-phosphate, plasma membrane, lipid binding protein
• 由来する生物種: Mus musculus (mouse)
• 細胞内の位置: Cytoplasm: Q6EDY6
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 299388.52

構造登録者

Zwolak, A.,Dominguez, R. (登録日: 2013-04-04, 公開日: 2013-10-09, 最終更新日: 2024-11-27)

主引用文献

Zwolak, A.,Yang, C.,Feeser, E.A.,Michael Ostap, E.,Svitkina, T.,Dominguez, R.
CARMIL leading edge localization depends on a non-canonical PH domain and dimerization.
Nat Commun, 4:2523-2523, 2013

PubMed Abstract: CARMIL is an approximately 1,370-amino-acid cytoskeletal scaffold that has crucial roles in cell motility and tissue development through interactions with cytoskeletal effectors and regulation of capping protein at the leading edge. However, the mechanism of CARMIL leading edge localization is unknown. Here we show that CARMIL interacts directly with the plasma membrane through its amino-terminal region. The crystal structure of CARMIL1-668 reveals that this region harbours a non-canonical pleckstrin homology (PH) domain connected to a 16-leucine-rich repeat domain. Lipid binding is mediated by the PH domain, but is further enhanced by a central helical domain. Small-angle X-ray scattering reveals that the helical domain mediates antiparallel dimerization, properly positioning the PH domains for simultaneous membrane interaction. In cells, deletion of the PH domain impairs leading edge localization. The results support a direct membrane-binding mechanism for CARMIL localization at the leading edge, where it regulates cytoskeletal effectors and motility.

PubMed: 24071777
DOI: 10.1038/ncomms3523

実験手法

X-RAY DIFFRACTION (2.895 Å)