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SLAC National Accelerator Laboratory

The Long-sought Structure of α-Catenin Defines Its Functions for Cell-cell Interactions

June 2013 SSRL Science Summary by Manuel Gnida, SLAC Office of Communications

Full-length α-catenin crystal structure reveals its dimeric asymmetric arrangement. The individual domains are colored individually (dimerization domain in yellow, vinculin binding domain in green, M-fragment in cyan, and the F-actin binding domain in magenta). A: View onto the vinculin binding domains. B: View onto the dimerization domains.

Cell-cell interactions play an important role in the development, architecture, maintenance, and function of tissues in all higher organisms. Cells use specialized protein complexes to bind each other. These complexes define the attachment sites known as adherens junctions and consist of three different proteins: cadherin, β-catenin, and α-catenin. Cadherin receptors are transmembrane proteins, whose domains on the outside of a cell direct the cell’s binding to other cells. Their intracellular tail binds β-catenin, which, in turn, binds α-catenin. Finally, α-catenin binds to the cytoskeleton, thereby stabilizing the adherens junction. Researchers from The Scripps Research Institute, Florida, used SSRL’s Beam Line 11-1 to solve the protein structure of α-catenin and determine how α-catenin links the cadherin/b-catenin complex to the cytoskeleton.

In their study, published in the journal Nature Structural & Molecular Biology, Rangarajan and Izard reported the structure of nearly full-length human α-catenin at 3.7 Å resolution. The remote data collection robotics, tunability of wavelengths, and stable beam conditions at Beam Line 11-1 were key factors for the success of the experiment. In its unbound state, the researchers found α-catenin to be an asymmetric dimer, whose two distinct subunits create a binding site for a cytoskeletal protein called F-actin. However, binding of β-catenin to α-catenin disrupts the interaction of the two subunits so that F-actin can no longer bind. These findings explain previous observations that α-catenin can bind F-actin, but not F-actin and b-catenin at the same time.   

However, in cells, α-catenin binds F-actin and/or the cadherin/β-catenin complex. The researchers determined that another cytoskeletal protein known as vinculin is important for adherens junction stabilization. Unlike β-catenin, vinculin does not disrupt the α-catenin dimer. Moreover, both partners in the vinculin/α-catenin complex are able to bind to F-actin. The researchers therefore suggest that vinculin-binding may stabilize the binding of F-actin to the cadherin/β-catenin/α-catenin adhesion complex in cells.


Primary Citation

E. S. Rangarajan, T. Izard, “Dimer Asymmetry Defines α-catenin Interactions”, Nat. Struct. Mol. Biol. 20, 188 (2013), doi:10.1038/nsmb.2479.

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Tina Izard, The Scripps Research Institute Florida

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