Receptor heteromerization is a mechanism used by G protein-coupled receptors to diversify their properties and function. We previously demonstrated that these interactions occur through salt bridge formation between epitopes of the involved receptors. Recent studies claim that calmodulin (CaM) binds to an Arg rich epitope located in the amino-terminus of the dopamine D2 receptor third intracellular loop. This is the same epitope involved in adenosine A2A-D2 receptor heteromerization, through Coulombic interaction between the Arg residues and a phosphorylated serine (pS) located in the medial segment of the C-terminus of the A2A receptor. Mass spectrometric analysis indicates that an electrostatic interaction involving the D2 receptor Arg-rich epitope and several CaM acidic epitopes are mainly responsible for the D2 receptor-CaM binding. CaM could also form multiple noncovalent complexes by means of electrostatic interactions with an epitope localized in the proximal segment of the C-terminus of the A2A receptor. Ca2+ disrupted the binding of CaM to the D2 but not to the A2A receptor epitope, and CaM disrupted the electrostatic interactions between the D2 receptor epitope and the more distal A2A receptor epitope. A model is introduced with the possible functional implications of A2A-D2-CaM interactions. These in vitro findings imply a possible regulatory role for CaM in recepto heteromers formation.

How calmodulin interacts with the adenosine A 2A and the dopamine D 2 Receptors / A. S., Woods; D., Marcellino; S. N., Jackson; R., Franco; S., Ferré; Agnati, Luigi Francesco; K., Fuxe. - In: JOURNAL OF PROTEOME RESEARCH. - ISSN 1535-3893. - STAMPA. - 7:8(2008), pp. 3428-3434. [10.1021/pr8001782]

How calmodulin interacts with the adenosine A 2A and the dopamine D 2 Receptors

AGNATI, Luigi Francesco;
2008

Abstract

Receptor heteromerization is a mechanism used by G protein-coupled receptors to diversify their properties and function. We previously demonstrated that these interactions occur through salt bridge formation between epitopes of the involved receptors. Recent studies claim that calmodulin (CaM) binds to an Arg rich epitope located in the amino-terminus of the dopamine D2 receptor third intracellular loop. This is the same epitope involved in adenosine A2A-D2 receptor heteromerization, through Coulombic interaction between the Arg residues and a phosphorylated serine (pS) located in the medial segment of the C-terminus of the A2A receptor. Mass spectrometric analysis indicates that an electrostatic interaction involving the D2 receptor Arg-rich epitope and several CaM acidic epitopes are mainly responsible for the D2 receptor-CaM binding. CaM could also form multiple noncovalent complexes by means of electrostatic interactions with an epitope localized in the proximal segment of the C-terminus of the A2A receptor. Ca2+ disrupted the binding of CaM to the D2 but not to the A2A receptor epitope, and CaM disrupted the electrostatic interactions between the D2 receptor epitope and the more distal A2A receptor epitope. A model is introduced with the possible functional implications of A2A-D2-CaM interactions. These in vitro findings imply a possible regulatory role for CaM in recepto heteromers formation.
2008
7
8
3428
3434
How calmodulin interacts with the adenosine A 2A and the dopamine D 2 Receptors / A. S., Woods; D., Marcellino; S. N., Jackson; R., Franco; S., Ferré; Agnati, Luigi Francesco; K., Fuxe. - In: JOURNAL OF PROTEOME RESEARCH. - ISSN 1535-3893. - STAMPA. - 7:8(2008), pp. 3428-3434. [10.1021/pr8001782]
A. S., Woods; D., Marcellino; S. N., Jackson; R., Franco; S., Ferré; Agnati, Luigi Francesco; K., Fuxe
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/593317
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