6DUW

Crystal structure of the alpha-N-catenin actin-binding domain H1 mutant

Summary for 6DUW

• Entry DOI: 10.2210/pdb6duw/pdb
• Descriptor: Catenin alpha-2 (2 entities in total)
• Functional Keywords: five-helix bundle, f-actin-binding, mechanosensor, cell adhesion
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 28120.34

Authors

Ishiyama, N.,Ikura, M. (deposition date: 2018-06-22, release date: 2018-12-19, Last modification date: 2023-10-11)

Primary citation

Ishiyama, N.,Sarpal, R.,Wood, M.N.,Barrick, S.K.,Nishikawa, T.,Hayashi, H.,Kobb, A.B.,Flozak, A.S.,Yemelyanov, A.,Fernandez-Gonzalez, R.,Yonemura, S.,Leckband, D.E.,Gottardi, C.J.,Tepass, U.,Ikura, M.
Force-dependent allostery of the alpha-catenin actin-binding domain controls adherens junction dynamics and functions.
Nat Commun, 9:5121-5121, 2018

PubMed Abstract: α-catenin is a key mechanosensor that forms force-dependent interactions with F-actin, thereby coupling the cadherin-catenin complex to the actin cytoskeleton at adherens junctions (AJs). However, the molecular mechanisms by which α-catenin engages F-actin under tension remained elusive. Here we show that the α1-helix of the α-catenin actin-binding domain (αcat-ABD) is a mechanosensing motif that regulates tension-dependent F-actin binding and bundling. αcat-ABD containing an α1-helix-unfolding mutation (H1) shows enhanced binding to F-actin in vitro. Although full-length α-catenin-H1 can generate epithelial monolayers that resist mechanical disruption, it fails to support normal AJ regulation in vivo. Structural and simulation analyses suggest that α1-helix allosterically controls the actin-binding residue V796 dynamics. Crystal structures of αcat-ABD-H1 homodimer suggest that α-catenin can facilitate actin bundling while it remains bound to E-cadherin. We propose that force-dependent allosteric regulation of αcat-ABD promotes dynamic interactions with F-actin involved in actin bundling, cadherin clustering, and AJ remodeling during tissue morphogenesis.

PubMed: 30504777
DOI: 10.1038/s41467-018-07481-7

Experimental method

X-RAY DIFFRACTION (2.2 Å)