6D8C

Cryo-EM structure of FLNaABD E254K bound to phalloidin-stabilized F-actin

6D8C の概要

• エントリーDOI: 10.2210/pdb6d8c/pdb
• EMDBエントリー: 7831 7832 7833
• 関連するBIRD辞書のPRD_ID: PRD_002307
• 分子名称: Filamin-A, Actin, alpha skeletal muscle, Phalloidin, ... (5 entities in total)
• 機能のキーワード: actin-binding domain, actin crosslinker, structural protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 13
• 化学式量合計: 386378.54

構造登録者

Iwamoto, D.V.,Huehn, A.R.,Simon, B.,Huet-Calderwood, C.,Baldassarre, M.,Sindelar, C.V.,Calderwood, D.A. (登録日: 2018-04-26, 公開日: 2018-09-19, 最終更新日: 2023-11-15)

主引用文献

Iwamoto, D.V.,Huehn, A.,Simon, B.,Huet-Calderwood, C.,Baldassarre, M.,Sindelar, C.V.,Calderwood, D.A.
Structural basis of the filamin A actin-binding domain interaction with F-actin.
Nat. Struct. Mol. Biol., 25:918-927, 2018

PubMed Abstract: Actin-cross-linking proteins assemble actin filaments into higher-order structures essential for orchestrating cell shape, adhesion, and motility. Missense mutations in the tandem calponin homology domains of their actin-binding domains (ABDs) underlie numerous genetic diseases, but a molecular understanding of these pathologies is hampered by the lack of high-resolution structures of any actin-cross-linking protein bound to F-actin. Here, taking advantage of a high-affinity, disease-associated mutant of the human filamin A (FLNa) ABD, we combine cryo-electron microscopy and functional studies to reveal at near-atomic resolution how the first calponin homology domain (CH1) and residues immediately N-terminal to it engage actin. We further show that reorientation of CH2 relative to CH1 is required to avoid clashes with actin and to expose F-actin-binding residues on CH1. Our data explain localization of disease-associated loss-of-function mutations to FLNaCH1 and gain-of-function mutations to the regulatory FLNaCH2. Sequence conservation argues that this provides a general model for ABD-F-actin binding.

PubMed: 30224736
DOI: 10.1038/s41594-018-0128-3

実験手法

ELECTRON MICROSCOPY (3.54 Å)