9JIH

Crystal structure of BAR domain of ACAP4

9JIH の概要

• エントリーDOI: 10.2210/pdb9jih/pdb
• 分子名称: Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3 (1 entity in total)
• 機能のキーワード: arfgap, tumor-associated, membrane bind cell migration, cancer metastasis, signaling protein
• 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: 63577.90

構造登録者

Huang, S.,Chen, J.S.,Wang, C. (登録日: 2024-09-11, 公開日: 2026-01-14, 最終更新日: 2026-04-01)

主引用文献

Huang, S.,Chen, J.,Wang, X.,Song, X.,Zhu, X.,Fu, C.,Zhang, X.,Liu, X.,Wang, C.
BAR-PH tandem of ACAP4 remodels membranes to drive migration via Ezrin-dependent activation.
J Mol Cell Biol, 17:-, 2026

PubMed Abstract: ADP-ribosylation factor (Arf)-specific GTPase-activating proteins (ArfGAPs) regulate cell migration through interactions with small G proteins, including Arfs. In ArfGAPs, the Bin/Amphiphysin/Rvs (BAR) domain plays a key role in membrane binding and curvature induction, yet the molecular mechanisms underlying these processes remain unclear. Here, we investigate the function of the BAR domain and its adjacent pleckstrin homology (PH) domain of ACAP4 in cell migration. We demonstrate that the BAR-PH tandem of ACAP4 induces membrane curvature, promotes cell migration, forms condensates in vitro, and exhibits membrane-associated distribution in cells. The crystal structure of the ACAP4 BAR domain, determined at 2.8 Å resolution, reveals multiple positively charged surface patches. Structural modeling further identifies conserved positively charged residue pairs in the PH domain, which collectively mediate electrostatic interactions essential for both membrane remodeling and membrane localization. Mutagenesis experiments confirm that these regions are required for ACAP4's subcellular localization and pro-migratory activity. Furthermore, we identify that the actin-binding protein Ezrin interacts with a specific C-terminal region of ACAP4 to regulate its function. Ezrin binding enhances condensate formation and enables full-length ACAP4 to associate with membranes and promote cell migration, particularly when co-expressed with the activated Ezrin (T567D). Together, our findings uncover the molecular basis by which ACAP4 coordinates membrane remodeling and cytoskeletal dynamics, offering new insights into the mechanisms that drive cell migration.

PubMed: 41190559
DOI: 10.1093/jmcb/mjaf038

実験手法

X-RAY DIFFRACTION (2.8 Å)