7KTW

Cryogenic electron microscopy model of full-length human metavinculin H1'-parallel conformation 2

7KTW の概要

• エントリーDOI: 10.2210/pdb7ktw/pdb
• 関連するPDBエントリー: 1TR2
• EMDBエントリー: 23029 23030 23031 23032
• 分子名称: metavinculin (1 entity in total)
• 機能のキーワード: actin, adaptor protein, cadherin, cancer, catenin, cell adhesion, cell junction, cell migration, cell signaling, focal adhesions, heart failure, inositol phospholipid, integrin, plasma membrane, skeletal muscle, smooth muscle
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 125061.50

構造登録者

Izard, T.,Rangarajan, E.S. (登録日: 2020-11-24, 公開日: 2021-01-27, 最終更新日: 2025-05-28)

主引用文献

Rangarajan, E.S.,Izard, T.
The Cryogenic Electron Microscopy Structure of the Cell Adhesion Regulator Metavinculin Reveals an Isoform-Specific Kinked Helix in Its Cytoskeleton Binding Domain.
Int J Mol Sci, 22:-, 2021

PubMed Abstract: Vinculin and its heart-specific splice variant metavinculin are key regulators of cell adhesion processes. These membrane-bound cytoskeletal proteins regulate the cell shape by binding to several other proteins at cell-cell and cell-matrix junctions. Vinculin and metavinculin link integrin adhesion molecules to the filamentous actin network. Loss of both proteins prevents cell adhesion and cell spreading and reduces the formation of stress fibers, focal adhesions, or lamellipodia extensions. The binding of talin at cell-matrix junctions or of α-catenin at cell-cell junctions activates vinculin and metavinculin by releasing their autoinhibitory head-tail interaction. Once activated, vinculin and metavinculin bind F-actin via their five-helix bundle tail domains. Unlike vinculin, metavinculin has a 68-amino-acid insertion before the second α-helix of this five-helix F-actin-binding domain. Here, we present the full-length cryogenic electron microscopy structure of metavinculin that captures the dynamics of its individual domains and unveiled a hallmark structural feature, namely a kinked isoform-specific α-helix in its F-actin-binding domain. Our identified conformational landscape of metavinculin suggests a structural priming mechanism that is consistent with the cell adhesion functions of metavinculin in response to mechanical and cellular cues. Our findings expand our understanding of metavinculin function in the heart with implications for the etiologies of cardiomyopathies.

PubMed: 33440717
DOI: 10.3390/ijms22020645

実験手法

ELECTRON MICROSCOPY (4.27 Å)