Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Combined computational and structural approach into understanding the role of peptide binding and activation of melanocortin receptor 4
Δημιουργός/Συγγραφέας:	Zachmann, Julian Kritsi, Eftichia Tapeinou, Anthi [EL] Ζουμπουλάκης, Παναγιώτης[EN] Zoumpoulakis, Panagiotis Tselios, Theodore Matsoukas, Minos-Timotheos
Εκδότης:	American Chemical Society
Ημερομηνία:	2020-03-23
Γλώσσα:	Αγγλικά
ISSN:	1549-9596 1549-960X
DOI:	10.1021/acs.jcim.9b01196
Άλλο:	31944109
Περίληψη:	Melanocortin receptor 4 (MC4R) is expressed predominantly in the central nervous system and regulates food intake and sexual function and is also thought to be responsible for effects on mood and cognition. It belongs to the melanocortin receptor subfamily of G protein-coupled receptors (GPCRs). Here, we have synthesized and structurally characterized three peptides that bind to MC4R, producing different signaling events. AgRP is a naturally occurring antagonist, HLWNRS is the minimal sequence of the N-terminal with partial agonist activity, and aMSH is a full agonistic peptide. By implementing molecular dynamics simulations on the different peptide-receptor complexes, we propose their molecular basis of binding to investigate their differential molecular properties regarding the activation states of the receptor. Our analysis shows that the agonist and partial agonist may induce rotation in transmembrane helix 3, which is known to be involved in the key events occurring during GPCR activation, and this movement is impacted by certain aromatic residues and their positioning in the orthosteric binding site of the receptor.
Τίτλος πηγής δημοσίευσης:	Journal of chemical information and modeling
Τόμος/Κεφάλαιο:	60
Τεύχος:	3
Σελίδες:	1461–1468
Θεματική Κατηγορία:	[EL] Χημική Βιολογία[EN] Chemical Biology [EL] Δομική Βιολογία[EN] Structural Biology
Λέξεις-Κλειδιά:	Amino Acid Sequence Cyclic AMP Molecular Dynamics Simulation Peptides Receptor, Melanocortin, Type 4
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2020, American Chemical Society
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://pubs.acs.org/doi/10.1021/acs.jcim.9b01196
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://pubs.acs.org/toc/jcisd8/60/3
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο