The myosin binding protein is a novel mineralocorticoid receptor binding partner.
The mineralocorticoid receptor (MR) plays a role in congestive heart failure; however, the molecular mechanism(s) remains undefined. We hypothesized that interaction of the MR with a cardiac protein modulates the transcriptional activation function of the MR within the heart. We used the yeast two-hybrid technique to screen a human heart library and found an aldosterone-dependent interaction between the hMR and the cardiac myosin binding protein (cMBP-c). The EC(50) of the hMR-MBP-c interaction was approximately 80nM, and the cMBP-c did not interact with the glucocorticoid receptor (GR). The GST pull-down technique was used to confirm an interaction between the MR and the cMBP-c as well as the lack of interaction with the GR. Spironolactone partially blocked this interaction, further suggesting MR specificity. We also determined the cMBP-c binding site lies within the C-terminus of the MR. We propose that interaction of the MR with cMBP-c may play a role in cardiac remodeling.
Bratton
Melyssa R
MR
Department of Medicine, Division of Endocrinology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA.
Gomez-Sanchez
Elise P
EP
Gomez-Sanchez
Celso E
CE
Subauste
Jose S
JS
D000450:Aldosterone / Q000494:pharmacology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D015723:Gene Library; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000187:drug effects / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D015003:Yeasts; D000099163:Myosin Binding Protein C
D000450:Aldosterone; D002352:Carrier Proteins; D018076:DNA, Complementary; D018161:Receptors, Mineralocorticoid; D000099163:Myosin Binding Protein C