Journal
JOURNAL OF PROTEOME RESEARCH
Volume 7, Issue 8, Pages 3428-3434Publisher
AMER CHEMICAL SOC
DOI: 10.1021/pr8001782
Keywords
calmodulin; dopamine D-2 receptor; adenosine A(2A) receptor; receptor heteromers; mass spectrometry
Categories
Funding
- Intramural NIH HHS [Z99 DA999999] Funding Source: Medline
Ask authors/readers for more resources
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 D-2 receptor third intracellular loop. This is the same epitope involved in adenosine A(2A)-D-2 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 A(2A) receptor. Mass spectrometric analysis indicates that an electrostatic interaction involving the D, receptor Arg-rich epitope and several CaM acidic epitopes are mainly responsible for the D-2 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 A(2A) receptor. Ca2+ disrupted the binding of CaM to the D-2 but not to the A(2A) receptor epitope, and CaM disrupted the electrostatic interactions between the D-2 receptor epitope and the more distal A(2A) receptor epitope. A model is introduced with the possible functional implications of A(2A)(-) D-2-CaM interactions. These in vitro findings imply a possible regulatory role for CaM in receptor heteromers formation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available