1l4t
From Proteopedia
(New page: 200px<br /> <applet load="1l4t" size="450" color="white" frame="true" align="right" spinBox="true" caption="1l4t" /> '''SOLUTION NMR STRUCTURE OF THE CCK2E3'''<br ...) |
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| - | [[Image:1l4t.gif|left|200px]]<br /> | + | [[Image:1l4t.gif|left|200px]]<br /><applet load="1l4t" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1l4t" size=" | + | |
caption="1l4t" /> | caption="1l4t" /> | ||
'''SOLUTION NMR STRUCTURE OF THE CCK2E3'''<br /> | '''SOLUTION NMR STRUCTURE OF THE CCK2E3'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The structure of the third extracellular loop of the human | + | 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 interactions with TM6. These differences may play a role in the ligand specificity displayed by the CCK1 and CCK2 receptor subtypes. |
==About this Structure== | ==About this Structure== | ||
| - | 1L4T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with ACE and NH2 as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1L4T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=ACE:'>ACE</scene> and <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1L4T OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Giragossian, C.]] | [[Category: Giragossian, C.]] | ||
| - | [[Category: Mierke, D | + | [[Category: Mierke, D F.]] |
[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: NH2]] | [[Category: NH2]] | ||
[[Category: hormone/growth factor receptor]] | [[Category: hormone/growth factor receptor]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:41:18 2008'' |
Revision as of 11:41, 21 February 2008
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SOLUTION NMR STRUCTURE OF THE CCK2E3
Overview
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 interactions with TM6. These differences may play a role in the ligand specificity displayed by the CCK1 and CCK2 receptor subtypes.
About this Structure
1L4T is a Single protein structure of sequence from [1] with and as ligands. Full crystallographic information is available from OCA.
Reference
Intermolecular interactions between cholecystokinin-8 and the third extracellular loop of the cholecystokinin-2 receptor., Giragossian C, Mierke DF, Biochemistry. 2002 Apr 9;41(14):4560-6. PMID:11926817
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