Structure of the Dimerization and β-Catenin- Binding Region of α-Catenin

In adherens junctions, alpha-catenin links the cadherin-beta-catenin complex to the actin-based cytoskeleton. alpha-catenin is a homodimer in solution, but forms a 1:1 heterodimer with beta-catenin. The crystal structure of the alpha-catenin dimerization domain, residues 82-279, shows that alpha-catenin dimerizes through formation of a four-helix bundle in which two antiparallel helices are contributed by each protomer. A slightly larger fragment, comprising residues 57-264, binds to beta-catenin. A chimera consisting of the alpha-catenin-binding region of beta-catenin linked to the amino terminus of alpha-catenin 57-264 behaves as a monomer in solution, as expected, since beta-catenin binding disrupts the alpha-catenin dimer. The crystal structure of this chimera reveals the interaction between alpha- and beta-catenin, and provides a basis for understanding adherens junction assembly.

[1]  P. Kraulis A program to produce both detailed and schematic plots of protein structures , 1991 .

[2]  B. Gumbiner,et al.  Molecular and functional analysis of cadherin-based adherens junctions. , 1997, Annual review of cell and developmental biology.

[3]  W J Nelson,et al.  Defining interactions and distributions of cadherin and catenin complexes in polarized epithelial cells , 1994, The Journal of cell biology.

[4]  J. S. Morrow,et al.  Molecular Cloning Reveals Alternative Splice Forms of Human α(E)-Catenin , 1994 .

[5]  M. Ozawa,et al.  Identification of the Domain of α-Catenin Involved in Its Association with β-Catenin and Plakoglobin (γ-Catenin)* , 1997, The Journal of Biological Chemistry.

[6]  S. Butz,et al.  Distinct cadherin—catenin complexes in Ca2+ dependent cell—cell adhesion , 1994, FEBS letters.

[7]  William I. Weis,et al.  Three-Dimensional Structure of the Armadillo Repeat Region of β-Catenin , 1997, Cell.

[8]  K. Johnson,et al.  Characterization of the interactions of alpha-catenin with alpha-actinin and beta-catenin/plakoglobin. , 1997, Journal of cell science.

[9]  M. Takeichi,et al.  Dynamic behavior of the cadherin-based cell-cell adhesion system during Drosophila gastrulation. , 1998, Developmental biology.

[10]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[11]  N. Copeland,et al.  Mouse αN-Catenin: Two Isoforms, Specific Expression in the Nervous System, and Chromosomal Localization of the Gene , 1994 .

[12]  S. Troyanovsky,et al.  Adhesive But Not Lateral E-cadherin Complexes Require Calcium and Catenins for Their Formation , 1998, The Journal of cell biology.

[13]  T. Uemura,et al.  α-Catenin-Vinculin Interaction Functions to Organize the Apical Junctional Complex in Epithelial Cells , 1998, The Journal of cell biology.

[14]  H. Aberle,et al.  Single Amino Acid Substitutions in Proteins of the armadillo Gene Family Abolish Their Binding to -Catenin (*) , 1996, The Journal of Biological Chemistry.

[15]  J. Engel,et al.  Homophilic adhesion of E‐cadherin occurs by a co‐operative two‐step interaction of N‐terminal domains. , 1996, The EMBO journal.

[16]  J. Papkoff,et al.  Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly , 1994, The Journal of cell biology.

[17]  S. Hirohashi,et al.  Identification of a neural α-catenin as a key regulator of cadherin function and multicellular organization , 1992, Cell.

[18]  M. Rothkegel,et al.  The molecular architecture of focal adhesions. , 1995, Annual review of cell and developmental biology.

[19]  R. Read,et al.  Improved Structure Refinement Through Maximum Likelihood , 1996 .

[20]  S. Kuroda,et al.  Cdc42 and Rac1 Regulate the Interaction of IQGAP1 with β-Catenin* , 1999, The Journal of Biological Chemistry.

[21]  B. Geiger,et al.  Primary sequence and domain structure of chicken vinculin. , 1989, The Biochemical journal.

[22]  A T Brünger,et al.  Direct Observation of Protein Solvation and Discrete Disorder with Experimental Crystallographic Phases , 1996, Science.

[23]  H. Aberle,et al.  Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor , 1994, The Journal of cell biology.

[24]  M. Peifer,et al.  Drosophila α-Catenin and E-cadherin Bind to Distinct Regions of Drosophila Armadillo* , 1996, The Journal of Biological Chemistry.

[25]  F. Lottspeich,et al.  The uvomorulin-anchorage protein alpha catenin is a vinculin homologue. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[26]  M Kokkinidis,et al.  Structure of the ColE1 rop protein at 1.7 A resolution. , 1987, Journal of molecular biology.

[27]  M. Krohn,et al.  A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin. , 1997, Journal of cell science.

[28]  M. Ringwald,et al.  Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[29]  B. Gumbiner,et al.  Lateral dimerization is required for the homophilic binding activity of C-cadherin , 1996, The Journal of cell biology.

[30]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[31]  Z. Otwinowski,et al.  [20] Processing of X-ray diffraction data collected in oscillation mode. , 1997, Methods in enzymology.

[32]  M. Krohn,et al.  A specific domain in α-catenin mediates binding to β-catenin or plakoglobin , 1997 .

[33]  J. Daniel,et al.  Tyrosine phosphorylation and cadherin/catenin function , 1997, BioEssays : news and reviews in molecular, cellular and developmental biology.

[34]  J. Zou,et al.  Improved methods for building protein models in electron density maps and the location of errors in these models. , 1991, Acta crystallographica. Section A, Foundations of crystallography.

[35]  B. Geiger,et al.  Immunoelectron microscope studies of membrane-microfilament interactions: distributions of alpha-actinin, tropomyosin, and vinculin in intestinal epithelial brush border and chicken gizzard smooth muscle cells , 1981, The Journal of cell biology.

[36]  M. Takeichi,et al.  Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin. , 1989, Cell regulation.

[37]  R. Kemler,et al.  Altered Cell Adhesion Activity by Pervanadate Due to the Dissociation of α-Catenin from the E-Cadherin·Catenin Complex* , 1998, The Journal of Biological Chemistry.

[38]  B. Jockusch,et al.  Vinculin Is Part of the Cadherin–Catenin Junctional Complex: Complex Formation between α-Catenin and Vinculin , 1998, The Journal of cell biology.

[39]  D L Rimm,et al.  Alpha 1(E)-catenin is an actin-binding and -bundling protein mediating the attachment of F-actin to the membrane adhesion complex. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[40]  M. Takeichi,et al.  Transmembrane control of cadherin-mediated cell-cell adhesion. , 1993, Seminars in cell biology.

[41]  M. Takeichi,et al.  The 102 kd cadherin-associated protein: Similarity to vinculin and posttranscriptional regulation of expression , 1991, Cell.

[42]  D. Rimm,et al.  α-Catenin Can Form Asymmetric Homodimeric Complexes and/or Heterodimeric Complexes with β-Catenin* , 1997, The Journal of Biological Chemistry.

[43]  W A Hendrickson,et al.  Selenomethionyl proteins produced for analysis by multiwavelength anomalous diffraction (MAD): a vehicle for direct determination of three‐dimensional structure. , 1990, The EMBO journal.

[44]  A. P. Soler,et al.  Interaction of alpha-actinin with the cadherin/catenin cell-cell adhesion complex via alpha-catenin , 1995, The Journal of cell biology.

[45]  Collaborative Computational,et al.  The CCP4 suite: programs for protein crystallography. , 1994, Acta crystallographica. Section D, Biological crystallography.

[46]  J. Thornton,et al.  PROCHECK: a program to check the stereochemical quality of protein structures , 1993 .

[47]  H Weissig,et al.  Assembly of the cadherin-catenin complex in vitro with recombinant proteins. , 1994, Journal of cell science.

[48]  K D Cowtan,et al.  Phase combination and cross validation in iterated density-modification calculations. , 1996, Acta crystallographica. Section D, Biological crystallography.

[49]  S. Ishihara,et al.  The roles of catenins in the cadherin-mediated cell adhesion: functional analysis of E-cadherin-alpha catenin fusion molecules , 1994, The Journal of cell biology.