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  The Architecture of Talin1 Reveals an Autoinhibition Mechanism

Dedden, D., Schumacher, S., Kelley, C., Zacharias, M., Biertümpfel, C., Fässler, R., et al. (2019). The Architecture of Talin1 Reveals an Autoinhibition Mechanism. CELL, 179(1), 120-131.e13. doi:10.1016/j.cell.2019.08.034.

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1-s2.0-S0092867419309535-main.pdf (Any fulltext), 7MB
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 Creators:
Dedden, Dirk1, 2, Author              
Schumacher, Stephanie1, Author              
Kelley, Charlotte1, Author              
Zacharias, Martin3, Author
Biertümpfel, Christian1, 4, Author              
Fässler, Reinhard5, Author              
Mizuno, Naoko1, 2, Author              
Affiliations:
1Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565144              
2Mizuno, Naoko / Cellular and Membrane Trafficking, Max Planck Institute of Biochemistry, Max Planck Society, ou_1688137              
3external, ou_persistent22              
4Biertümpfel, Christian / Molecular Mechanisms of DNA Repair, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565143              
5Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

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Free keywords: INTEGRIN ACTIVATION; FERM DOMAIN; NANOSCALE ARCHITECTURE; VINCULIN ACTIVATION; STRUCTURAL BASIS; BINDING DOMAIN; CRYO-EM; ADHESION; HEAD; SITESBiochemistry & Molecular Biology; Cell Biology;
 Abstract: Focal adhesions (FAs) are protein machineries essential for cell adhesion, migration, and differentiation. Talin is an integrin-activating and tension-sensing FA component directly connecting integrins in the plasma membrane with the actomyosin cytoskeleton. To understand how talin function is regulated, we determined a cryoelectron microscopy (cryo-EM) structure of full-length talin1 revealing a two-way mode of autoinhibition. The actin-binding rod domains fold into a 15-nm globular arrangement that is interlocked by the integrin-binding FERM head. In turn d domains R9 and R12 shield access of the FERM domain to integrin and the phospholipid PIP2 at the membrane. This mechanism likely ensures synchronous inhibition of integrin, membrane, and cytoskeleton binding. We also demonstrate that compacted talin1 reversibly unfolds to an similar to 60-nm string-like conformation, revealing interaction sites for vinculin and actin. Our data explain how fast switching between active and inactive conformations of talin could regulate FA turnover, a process critical for cell adhesion and signaling.

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Language(s): eng - English
 Dates: 2019-09-19
 Publication Status: Published in print
 Pages: 25
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: CELL
Source Genre: Journal
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Publ. Info: 50 HAMPSHIRE ST, FLOOR 5, CAMBRIDGE, MA 02139 USA : CELL PRESS
Pages: - Volume / Issue: 179 (1) Sequence Number: - Start / End Page: 120 - 131.e13 Identifier: ISSN: 0092-8674