Cardiac contractility structure-activity relationship and ligand-receptor interactions; the discovery of unique and novel molecular switches in myosuppressin signaling

PloS One
Megan LeanderRuthann Nichols

Abstract

Peptidergic signaling regulates cardiac contractility; thus, identifying molecular switches, ligand-receptor contacts, and antagonists aids in exploring the underlying mechanisms to influence health. Myosuppressin (MS), a decapeptide, diminishes cardiac contractility and gut motility. Myosuppressin binds to G protein-coupled receptor (GPCR) proteins. Two Drosophila melanogaster myosuppressin receptors (DrmMS-Rs) exist; however, no mechanism underlying MS-R activation is reported. We predicted DrmMS-Rs contained molecular switches that resembled those of Rhodopsin. Additionally, we believed DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 interactions would reflect our structure-activity relationship (SAR) data. We hypothesized agonist- and antagonist-receptor contacts would differ from one another depending on activity. Lastly, we expected our study to apply to other species; we tested this hypothesis in Rhodnius prolixus, the Chagas disease vector. Searching DrmMS-Rs for molecular switches led to the discovery of a unique ionic lock and a novel 3-6 lock, as well as transmission and tyrosine toggle switches. The DrmMS-DrmMS-R1 and DrmMS-DrmMS-R2 contacts suggested tissue-specific signaling existed, which was in line with our SAR data. We iden...Continue Reading

References

Aug 12, 1977·Science·D A Price, M J Greenberg
Feb 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Olaf FritzeOliver P Ernst
Aug 9, 2003·Proceedings of the National Academy of Sciences of the United States of America·Kristoffer EgerodCornelis J P Grimmelikhuijzen
Aug 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Jong-Myoung KimH Gobind Khorana
Jan 13, 2009·Proteomics·Sheila OnsRolando Rivera Pomar
Apr 29, 2009·Journal of Computational Chemistry·Garrett M MorrisArthur J Olson
Jul 6, 2010·Biochemical and Biophysical Research Communications·Jasbir UpadhyayaPrashen Chelikani
Jul 31, 2010·Journal of the American Chemical Society·Daniel WackerRaymond C Stevens
Oct 21, 2010·Insect Molecular Biology·S OnsR Rivera-Pomar
Mar 11, 2011·Nature·Jörg StandfussGebhard F X Schertler
Jun 24, 2011·Nature·Tatsuro ShimamuraSo Iwata
Jul 5, 2011·Current Opinion in Structural Biology·Xavier Deupi, Jörg Standfuss
Feb 4, 2012·Current Medicinal Chemistry·B TrzaskowskiS Filipek
May 25, 2012·The Journal of Experimental Biology·Dohee LeeAngela B Lange

❮ Previous
Next ❯

Datasets Mentioned

BETA
KDR23127.1
EFA01374.1
EFx86411.1
ACI90287.1
ACI90288.1

Software Mentioned

Rs
TASSER
PyMOL Molecular Graphics System
AutoDockTools
PyMOL
ModRefiner
DrmMS
AutoDock Vina
GraphPad Prism

Related Concepts

Related Feeds

Bradyarrhythmias

Bradyarrhythmias are slow heart rates. Symptoms may include syncope, dizziness, fatigure, shortness of breath, and chest pains. Find the latest research on bradyarrhythmias here.