Next Article in Journal
Genetic Variations in Prostaglandin E2 Pathway Identified as Susceptibility Biomarkers for Gastric Cancer in an Intermediate Risk European Country
Previous Article in Journal
Elastic Electron Scattering from Methane Molecule in the Energy Range from 50–300 eV
Article

The Cryogenic Electron Microscopy Structure of the Cell Adhesion Regulator Metavinculin Reveals an Isoform-Specific Kinked Helix in Its Cytoskeleton Binding Domain

Cell Adhesion Laboratory, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, Jupiter, FL 33458, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 645; https://doi.org/10.3390/ijms22020645
Received: 16 December 2020 / Revised: 8 January 2021 / Accepted: 8 January 2021 / Published: 11 January 2021
(This article belongs to the Section Macromolecules)
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. View Full-Text
Keywords: actin; cadherin; cancer; catenin; cell adhesion; cell junction; cell migration; cell signaling; heart failure; integrin; plasma membrane actin; cadherin; cancer; catenin; cell adhesion; cell junction; cell migration; cell signaling; heart failure; integrin; plasma membrane
Show Figures

Figure 1

MDPI and ACS Style

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. 2021, 22, 645. https://doi.org/10.3390/ijms22020645

AMA Style

Rangarajan ES, Izard T. The Cryogenic Electron Microscopy Structure of the Cell Adhesion Regulator Metavinculin Reveals an Isoform-Specific Kinked Helix in Its Cytoskeleton Binding Domain. International Journal of Molecular Sciences. 2021; 22(2):645. https://doi.org/10.3390/ijms22020645

Chicago/Turabian Style

Rangarajan, Erumbi S., and Tina Izard. 2021. "The Cryogenic Electron Microscopy Structure of the Cell Adhesion Regulator Metavinculin Reveals an Isoform-Specific Kinked Helix in Its Cytoskeleton Binding Domain" International Journal of Molecular Sciences 22, no. 2: 645. https://doi.org/10.3390/ijms22020645

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop