1hzn
From Proteopedia
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NMR SOLUTION STRUCTURE OF THE THIRD EXTRACELLULAR LOOP OF THE CHOLECYSTOKININ A RECEPTOR
Overview
The interaction of the C-terminal octapeptide of cholecystokinin, CCK-8, with the third extracellular loop of human cholecystokinin-A receptor, CCK(A)-R(329-357), has been probed by high-resolution NMR and extensive, computer simulations. The structure of CCK(A)-R(329-357) in the presence, of dodecylphosphocholine micelles consists of three alpha-helices, with, the first and third corresponding to the extracellular ends of, transmembrane (TM) helices 6 and 7. The central helix, residues W335-R345, is found to lie on the zwitterionic surface. Titration with CCK-8 produces, a stable complex with a number of intermolecular NOEs between the, C-terminus of the ligand (Trp(30), Met(31), Asp(32)) and the interface of, TM6 and the third extracellular loop (N333, A334, Y338) of the receptor, fragment. The mode of ligand binding based on these intermolecular NOEs is, in agreement with a number of published findings from receptor mutagenesis, and photoaffinity cross-linking. Utilizing these ligand/receptor points of, interaction, the structural features of CCK(A)-R(329-357), and also the, structures of CCK-8 and CCK(A)-R(1-47) previously determined, extensive, molecular dynamics simulations of the CCK-8/CCK(A)-R complex were carried, out. The results provide unique insight into the molecular interactions, and forces important for the binding of CCK-8 to CCK(A)-R.
About this Structure
1HZN is a Single protein structure of sequence from [1] with ACE and NH2 as ligands. Full crystallographic information is available from OCA.
Reference
Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin A receptor., Giragossian C, Mierke DF, Biochemistry. 2001 Apr 3;40(13):3804-9. PMID:11300760
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