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Dimer asymmetry defines α-catenin interactions

Nature Structural & Molecular Biology volume 20, pages 188–193 (2013)Cite this article

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Abstract

The F-actin–binding cytoskeletal protein α-catenin interacts with β-catenin–cadherin complexes and stabilizes cell-cell junctions. The β-catenin–α-catenin complex cannot bind F-actin, whereas interactions of α-catenin with the cytoskeletal protein vinculin appear to be necessary to stabilize adherens junctions. Here we report the crystal structure of nearly full-length human α-catenin at 3.7-Å resolution. α-catenin forms an asymmetric dimer where the four-helix bundle domains of each subunit engage in distinct intermolecular interactions. This results in a left handshake–like dimer, wherein the two subunits have remarkably different conformations. The crystal structure explains why dimeric α-catenin has a higher affinity for F-actin than does monomeric α-catenin, why the β-catenin–α-catenin complex does not bind F-actin, how activated vinculin links the cadherin–catenin complex to the cytoskeleton and why α-catenin but not inactive vinculin can bind F-actin.

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Figure 1: α-catenin structure.
Figure 2: α-catenin is a dimer that resembles a left handshake.
Figure 3: Model of the α-catenin–β-catenin heterodimer based on the crystal structures of β-catenin (PDB 2Z6G, shown as a cartoon and surface, both in green), the α-catenin–β-catenin chimera (PDB 1DOW, shown as a cartoon in pink) and α-catenin subunits A (cyan) or B (gray) shown as a cartoon in a or b, respectively, and as a gray surface.
Figure 4: The F-actin–binding domain surfaces of vinculin and dimeric α-catenin are distinct.
Figure 5: Asymmetry also directs interactions of α-catenin with vinculin.

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Acknowledgements

We are indebted to our colleagues at Scripps Florida: J. Cleveland for discussions and critical review of the manuscript, Z. Wu and P. Bois for sequencing and P. Bois for fruitful discussions. We thank C. Vonrhein and G. Bricogne (Global Phasing Ltd.) for analyses and helpful discussions. We are grateful to the staff at the SER-CAT (BM22) and SSRL (11-1) for synchrotron support. T.I. is supported by grants from the US National Institute of General Medical Sciences from the US National Institutes of Health (GM071596 and GM094483) and by start-up funds provided to Scripps Florida from the State of Florida. This is publication no. 21863 from The Scripps Research Institute.

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  1. Department of Cancer Biology, Scripps Research Institute, Jupiter, Florida, USA

    Erumbi S Rangarajan & Tina Izard

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Both authors contributed to the design and interpretation of all aspects of this work. E.S.R. performed all of the experiments. T.I. wrote the manuscript.

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Correspondence to Tina Izard.

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Rangarajan, E., Izard, T. Dimer asymmetry defines α-catenin interactions. Nat Struct Mol Biol 20, 188–193 (2013). https://doi.org/10.1038/nsmb.2479

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