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

104 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
Externally publishedYes

Fingerprint

Occludin
Tight Junction Proteins
Adherens Junctions
Catenins
Herpes Zoster
Proteins
Tight Junctions
Hinges
Zonula Occludens-1 Protein
Molecular Models
Peptide Mapping
Surface Plasmon Resonance
Surface plasmon resonance
Molecular Structure
Epitopes
Spectrum Analysis
Crystal structure
Binding Sites
Spectroscopy

ASJC Scopus subject areas

  • Biochemistry

Cite this

The tight junction protein occludin and the adherens junction protein α-catenin share a common interaction mechanism with ZO-1 *. / Müller, Sebastian L.; Portwich, Michael; Schmidt, Anke; Utepbergenov, Darkhan I.; Huber, Otmar; Blasig, Ingolf E.; Krause, Gerd.

In: Journal of Biological Chemistry, Vol. 280, No. 5, 04.02.2005, p. 3747-3756.

Research output: Contribution to journalArticle

Müller, Sebastian L. ; Portwich, Michael ; Schmidt, Anke ; Utepbergenov, Darkhan I. ; Huber, Otmar ; Blasig, Ingolf E. ; Krause, Gerd. / The tight junction protein occludin and the adherens junction protein α-catenin share a common interaction mechanism with ZO-1 *. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 5. pp. 3747-3756.
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