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 language | English |
|---|---|
| Pages (from-to) | 3747-3756 |
| Number of pages | 10 |
| Journal | Journal of Biological Chemistry |
| Volume | 280 |
| Issue number | 5 |
| DOIs | |
| Publication status | Published - Feb 4 2005 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - The tight junction protein occludin and the adherens junction protein α-catenin share a common interaction mechanism with ZO-1 *
AU - Müller, Sebastian L.
AU - Portwich, Michael
AU - Schmidt, Anke
AU - Utepbergenov, Darkhan I.
AU - Huber, Otmar
AU - Blasig, Ingolf E.
AU - Krause, Gerd
PY - 2005/2/4
Y1 - 2005/2/4
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M411365200
DO - 10.1074/jbc.M411365200
M3 - Article
VL - 280
SP - 3747
EP - 3756
JO - Journal of Biological Chemistry
T2 - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 5
ER -