The Long-sought Structure of α-Catenin Defines Its Functions for Cell-cell Interactions
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.
Related Links
- Science Highlight – HTML / PDF
- SSRL Science Highlights Archive
- SSRL Beam Lines
- The Scripps Research Institute News Release
Contact
Tina Izard, The Scripps Research Institute Florida
