The tight junction protein occludin and the adherens junction protein α-catenin share a common interaction mechanism with ZO-1 *

Sebastian L. Müller, Michael Portwich, Anke Schmidt, Darkhan I. Utepbergenov, Otmar Huber, Ingolf E. Blasig, Gerd Krause

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The exact sites, structures, and molecular mechanisms of interaction between junction organizing zona occludence protein 1 (ZO-1) and the tight junction protein occludin or the adherens junction protein α-catenin are unknown. Binding studies by surface plasmon resonance spectroscopy and peptide mapping combined with comparative modeling utilizing crystal structures led for the first time to a molecular model revealing the binding of both occludin and α-catenin to the same binding site in ZO-1. Our data support a concept that ZO-1 successively associates with α-catenin at the adherens junction and occludin at the tight junction. Strong spatial evidence indicates that the occludin C-terminal coiled-coil domain dimerizes and interacts finally as a four-helix bundle with the identified structural motifs in ZO-1. The helix bundle of occludin406-521 and α-catenin509-906 interacts with the hinge region (ZO-1591-632 and ZO-1 591-622, respectively) and with (ZO-1726-754 and ZO-1 756-781) in the GuK domain of ZO-1 containing coiled-coil and α-helical structures, respectively. The selectivity of both protein-protein interactions is defined by complementary shapes and charges between the participating epitopes. In conclusion, a common molecular mechanism of forming an intermolecular helical bundle between the hinge region/GuK domain of ZO-1 and α-catenin and occludin is identified as a general molecular principle organizing the association of ZO-1 at adherens and tight junctions.

Original languageEnglish
Pages (from-to)3747-3756
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number5
DOIs
Publication statusPublished - Feb 4 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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