Biochemical studies and Molecular Dynamics Simulations of Smad3-Erbin interaction identify a non-classical Erbin PDZ binding

Nadine Déliot; Matthieu Chavent; Claire Nourry; P. LÉcine; C. Arnaud; A. Hermant; Bernard Maigret; Jp Borg

inria-00339128, version 1

Biochemical studies and Molecular Dynamics Simulations of Smad3-Erbin interaction identify a non-classical Erbin PDZ binding

Nadine Déliot, Matthieu Chavent ¹, Claire Nourry, P. LÉcine, C. Arnaud, A. Hermant ², Bernard Maigret ¹, Jp Borg ³

Biochemical and Biophysical Research Communications / Biochemistry and Biophysics Research Communications 378, 3 (2009) 360-365

Résumé : In this work, we describe how the Erbin PDZ domain interacts with Smad3, a transductor of the Transforming Growth Factor-beta (TGFbeta) pathway, via its MH2 domain. This interaction was described as important for TGFbeta signaling as it could potentially repress the transcriptional activity of the growth factor. In order to clarify our preliminary experimental observations pointing this interaction, we built a 3D model of the Erbin PDZ/Smad3 MH2 complex and checked its stability using molecular dynamics simulations. This model pointed out charged residues in Smad3 and Erbin which could be important for the interaction. By introducing point mutations of these residues within the proposed binding domains, we experimentally confirmed that arginine 279, glutamic acid 246 in Smad3 and glutamic acid 1321 in Erbin are important for the binding. These data suggest a possible novel interface of binding in the Erbin PDZ domain and reveal an unconventional mode of interaction for a PDZ domain and its ligand.

1 : ORPAILLEUR (INRIA Lorraine - LORIA)
INRIA – CNRS : UMR7503 – Université Henri Poincaré - Nancy I – Université Nancy II – Institut National Polytechnique de Lorraine (INPL)
2 : Cytokines, hématopoïèse et réponse immune (CHRI)
CNRS : UMR8147 – Université Paris V - Paris Descartes
3 : Institut de Biologie du Développement de Marseille Luminy (IBDML)
CNRS : UMR6216 – Université de la Méditerranée - Aix-Marseille II

inria-00339128, version 1
http://hal.inria.fr/inria-00339128
oai:hal.inria.fr:inria-00339128
Contributeur : Malika Smail-Tabbone <>
Soumis le : Dimanche 16 Novembre 2008, 23:15:58
Dernière modification le : Lundi 23 Novembre 2009, 16:08:09

Voir la fiche détaillée

Exporter

Bibtex EndNote TEI RefWorks

%% inria-00339128, version 1
%% http://hal.inria.fr/inria-00339128
@article{deliot:inria-00339128,
    hal_id = {inria-00339128},
    url = {http://hal.inria.fr/inria-00339128},
    title = {{Biochemical studies and Molecular Dynamics Simulations of Smad3-Erbin interaction identify a non-classical Erbin PDZ binding}},
    author = {D{\'e}liot, Nadine and Chavent, Matthieu and Nourry, Claire and L{\'E}cine, P. and Arnaud, C. and Hermant, A. and Maigret, Bernard and Borg, Jp},
    abstract = {{In this work, we describe how the Erbin PDZ domain interacts with Smad3, a transductor of the Transforming Growth Factor-beta (TGFbeta) pathway, via its MH2 domain. This interaction was described as important for TGFbeta signaling as it could potentially repress the transcriptional activity of the growth factor. In order to clarify our preliminary experimental observations pointing this interaction, we built a 3D model of the Erbin PDZ/Smad3 MH2 complex and checked its stability using molecular dynamics simulations. This model pointed out charged residues in Smad3 and Erbin which could be important for the interaction. By introducing point mutations of these residues within the proposed binding domains, we experimentally confirmed that arginine 279, glutamic acid 246 in Smad3 and glutamic acid 1321 in Erbin are important for the binding. These data suggest a possible novel interface of binding in the Erbin PDZ domain and reveal an unconventional mode of interaction for a PDZ domain and its ligand.}},
    language = {Anglais},
    affiliation = {ORPAILLEUR - INRIA Lorraine - LORIA , Cytokines, h{\'e}matopo{\"\i}{\`e}se et r{\'e}ponse immune - CHRI , Institut de Biologie du D{\'e}veloppement de Marseille Luminy - IBDML},
    publisher = {Elsevier},
    pages = {360-365},
    journal = {Biochemical and Biophysical Research Communications / Biochemistry and Biophysics Research Communications},
    volume = {378},
    number = {3 },
    audience = {internationale },
    year = {2009},
}

<?xml version="1.0" encoding="UTF-8"?>
<listBibl xmlns="http://www.tei-c.org/ns/1.0" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML">
<listBibl type="article"><head>Articles dans des revues avec comité de lecture</head>
<biblStruct type="article" xml:id="inria-00339128"><analytic>
<author><persName><forename>Nadine</forename><surname>Déliot</surname></persName></author>
<author><persName><forename>Matthieu</forename><surname>Chavent</surname></persName>
<affiliation>
<orgName type="laboratory">INRIA Lorraine - LORIA</orgName>
<orgName type="team">ORPAILLEUR</orgName>
<country>FR</country>
<orgName type="institution">INRIA</orgName>
<orgName type="institution">CNRS : UMR7503</orgName>
<orgName type="institution">Université Henri Poincaré - Nancy I</orgName>
<orgName type="institution">Université Nancy II</orgName>
<orgName type="institution">Institut National Polytechnique de Lorraine (INPL)</orgName>
</affiliation>
</author>
<author><persName><forename>Claire</forename><surname>Nourry</surname></persName></author>
<author><persName><forename>P.</forename><surname>LÉcine</surname></persName></author>
<author><persName><forename>C.</forename><surname>Arnaud</surname></persName></author>
<author><persName><forename>A.</forename><surname>Hermant</surname></persName>
<affiliation>
<orgName type="laboratory">CHRI</orgName>
<orgName type="team">Cytokines, hématopoïèse et réponse immune</orgName>
<country>FR</country>
<orgName type="institution">CNRS : UMR8147</orgName>
<orgName type="institution">Université Paris V - Paris Descartes</orgName>
</affiliation>
</author>
<author><persName><forename>Bernard</forename><surname>Maigret</surname></persName>
<affiliation>
<orgName type="laboratory">INRIA Lorraine - LORIA</orgName>
<orgName type="team">ORPAILLEUR</orgName>
<country>FR</country>
<orgName type="institution">INRIA</orgName>
<orgName type="institution">CNRS : UMR7503</orgName>
<orgName type="institution">Université Henri Poincaré - Nancy I</orgName>
<orgName type="institution">Université Nancy II</orgName>
<orgName type="institution">Institut National Polytechnique de Lorraine (INPL)</orgName>
</affiliation>
</author>
<author><persName><forename>Jp</forename><surname>Borg</surname></persName>
<affiliation>
<orgName type="laboratory">IBDML</orgName>
<orgName type="team">Institut de Biologie du Développement de Marseille Luminy</orgName>
<country>FR</country>
<orgName type="institution">CNRS : UMR6216</orgName>
<orgName type="institution">Université de la Méditerranée - Aix-Marseille II</orgName>
</affiliation>
</author>
<title type="main" level="a">Biochemical studies and Molecular Dynamics Simulations of Smad3-Erbin interaction identify a non-classical Erbin PDZ binding</title></analytic><monogr><title level="j" type="main">Biochemical and Biophysical Research Communications / Biochemistry and Biophysics Research Communications</title><imprint><publisher>Elsevier</publisher><biblScope type="publicationDate">2009-00-00</biblScope><biblScope type="vol">378</biblScope><biblScope type="issue">3</biblScope><biblScope type="pp">360-365</biblScope></imprint></monogr><idno type="HALid">http://hal.inria.fr/inria-00339128</idno></biblStruct>
</listBibl>
</listBibl>