Molecular interactions of the physiological anti-hypertensive peptide catestatin with the neuronal nicotinic acetylcholine receptor

Journal of Cell Science
Bhavani S SahuNitish R Mahapatra

Abstract

Catestatin (CST), a chromogranin-A-derived peptide, is a potent endogenous inhibitor of the neuronal nicotinic acetylcholine receptor (nAChR). It exerts an anti-hypertensive effect by acting as a 'physiological brake' on transmitter release into the circulation. However, the mechanism of interaction of CST with nAChR is only partially understood. To unravel molecular interactions of the wild-type human CST (CST-WT) as well as its naturally occurring variants (CST-364S and CST-370L, which have Gly→Ser and Pro→Leu substitutions, respectively) with the human α3β4 nAChR, we generated a homology-modeled human α3β4 nAChR structure and solution structures of CST peptides. Docking and molecular dynamics simulations showed that ~90% of interacting residues were within 15 N-terminal residues of CST peptides. The rank order of binding affinity of these peptides with nAChR was: CST-370L>CST-WT>CST-364S; the extent of occlusion of the receptor pore by these peptides was also in the same order. In corroboration with computational predictions, circular dichroism analysis revealed significant differences in global structures of CST peptides (e.g. the order of α-helical content was: CST-370L>CST-WT>CST-364S). Consistently, CST peptides blocked ...Continue Reading

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Citations

Aug 20, 2014·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Zheng Wu, Dan Zhu
Jul 15, 2016·Biomarkers in Medicine·Yilin Zhao, Dan Zhu
Oct 8, 2019·Annals of the New York Academy of Sciences·Sushil K Mahata, Angelo Corti
Dec 20, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yasmina BourebabaLynda Bourebaba
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shinhui LeeJunho H Lee
Dec 12, 2020·Langmuir : the ACS Journal of Surfaces and Colloids·Soumik BardhanSanjib Senapati

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