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Characterization of multiple stable conformers of the EC5 domain of E-cadherin and the interaction of EC5 with E-cadherin peptides
Zheng, Kai Laurence, Jennifer S. Kuczera, Krzysztof Verkhivker, Gennady M. Middaugh, C. Russell Siahaan, Teruna J.
Zheng, Kai
Laurence, Jennifer S.
Kuczera, Krzysztof
Verkhivker, Gennady M.
Middaugh, C. Russell
Siahaan, Teruna J.
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Abstract
The objectives of this work were to express the EC5 domain of E-cadherin and determine its structural characteristics as well as to evaluate the binding properties of HAV and BLG4 peptides to EC5 using spectroscopic methods. Homophilic interactions of E-cadherins are responsible for cell-cell adhesion in the adherens junctions of the biological barriers (i.e., intestinal mucosa and
blood-brain barriers). The EC5 domain of E-cadherin has an important role in T-cell adhesion to intestinal mucosa via αEβ7 integrin-E-cadherin interactions. In this study, the expressed EC5 has a high thermal stability (Tm = 64.3 °C); it also has two stable conformations at room temperature, which convert to one conformation at approximately 54.5 °C. NMR and FTIR showed that HAV and BLG4 peptides bind to EC5. HSQC-NMR showed that either Asn or Gln of EC5 was involved in the interactions with HAV and BLG4 peptides. EC5 underwent a conformational change upon interaction with the HAV and BLG4 peptides. Finally, the binding properties of both peptides were modeled by docking experiments, and the results suggest that Asn-46 and Asn-75 of EC5 could be involved during the interaction with the peptides and that the Ser and Trp residues of the HAV and BLG4 peptides, respectively, were important for binding to EC5.
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Date
2009-06
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Publisher
Wiley
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Keywords
E-cadherin, EC5 domain, Conformation, Spectroscopy, Adherens junction, Cell-cell adhesion, Peptide binding
Citation
Zheng, K., Laurence, J. S., Kuczera, K., Verkhivker, G., Russell Middaugh, C. and Siahaan, T. J. (2009), Characterization of Multiple Stable Conformers of the EC5 Domain of E-cadherin and the Interaction of EC5 with E-cadherin Peptides. Chemical Biology & Drug Design, 73: 584–598. doi:10.1111/j.1747-0285.2009.00818.x