Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin-2 receptor

Biochemistry
Craig Giragossian, D F Mierke

Abstract

The structure of the third extracellular loop of the human cholecystokinin-2 receptor, CCK2-R(352-379), and its interactions with the C-terminal octapeptide of cholecystokinin (CCK-8) have been determined by high-resolution NMR and computer simulations. In the presence of dodecylphosphocholine micelles, the structure of the receptor fragment consisted of three helices, with the first and third corresponding to residues of the extracellular ends of transmembrane helices (TM) 6 and 7, respectively. The central, extracellular helix, consisting of residues 363-368, was found to be closely associated with the membrane mimetic used during the spectroscopic studies and molecular dynamics (MD) simulations. Upon titration of CCK-8 to the receptor domain, chemical shift perturbation and intermolecular NOEs (Trp30, Met31 of CCK-8 and P371, F374 of CCK2-R) indicated the formation of a stable complex and specific ligand/receptor interactions. Using the NOE-generated intermolecular contact points, extensive MD simulations of CCK-8 bound to the CCK2 receptor were carried out. The results, with CCK-8 in close proximity to TM7, differ from previous structural studies of CCK-8 association with CCK1-R, in which the ligand formed a number of inter...Continue Reading

References

Nov 1, 1992·Journal of Biomolecular NMR·M PiottoV Sklenár
Oct 15, 1984·Journal of Molecular Biology·D EisenbergR Wall
May 5, 1982·Journal of Molecular Biology·J Kyte, R F Doolittle
Aug 1, 1993·European Journal of Biochemistry·S Silvente-PoirotD Fourmy
Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Jan 18, 1996·European Journal of Pharmacology·A JagerschmidtB P Roques
May 28, 1998·The Journal of Biological Chemistry·E M HadacL J Miller
Apr 12, 2001·The British Journal of Surgery·M HenwoodS A Watson

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Citations

Jun 3, 2006·Natural Product Reports·Tara L PukalaMichael J Tyler
Nov 13, 2012·Journal of Biomolecular Structure & Dynamics·Grégory Da CostaJean-Pierre Monti
Jan 19, 2005·The FEBS Journal·Russell V BaudinetteJohn H Bowie
Apr 2, 2011·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·David N LangelaanJan K Rainey
Sep 21, 2004·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ettore BenedettiLuigi Aloj
Jun 23, 2009·Toxicon : Official Journal of the International Society on Toxinology·Patrick J ShermanJohn H Bowie
Sep 9, 2008·Journal of Molecular Graphics & Modelling·Kirandeep Kaur, Tanaji T Talele
Nov 14, 2006·Biochimica Et Biophysica Acta·Philip L Yeagle, Arlene D Albert
Feb 8, 2003·Annual Review of Biophysics and Biomolecular Structure·Slawomir FilipekRonald Stenkamp
May 23, 2003·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Bruno L VictorCláudio M Soares
Jan 19, 2008·Journal of Medicinal Chemistry·Caroline M R Low, J G Vinter

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