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1d6g

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(New page: 200px<br /> <applet load="1d6g" size="450" color="white" frame="true" align="right" spinBox="true" caption="1d6g" /> '''MOLECULAR COMPLEX OF CHOLECYSTOKININ-8 AND ...)
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'''MOLECULAR COMPLEX OF CHOLECYSTOKININ-8 AND N-TERMINUS OF THE CHOLECYSTOKININ A RECEPTOR BY NMR SPECTROSCOPY'''<br />
'''MOLECULAR COMPLEX OF CHOLECYSTOKININ-8 AND N-TERMINUS OF THE CHOLECYSTOKININ A RECEPTOR BY NMR SPECTROSCOPY'''<br />
==Overview==
==Overview==
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The bimolecular complex of the C-terminal octapeptide of cholecystokinin, CCK-8, with the N-terminus of the CCK(A)-receptor, CCK(A)-R(1-47), has, been structurally characterized by high-resolution NMR and computational, refinement. The conformation of CCK(A)-R(1-47), within the lipid, environment used for the spectroscopic studies, consists of a well-defined, alpha-helix (residues 3-9) followed by a beta-sheet stabilized by a, disulfide linkage between C18 and C29, leading to the first transmembrane, alpha-helix (TM1). Titration of CCK(A)-R(1-47) with CCK-8 specifically, affects the NMR signals of W39 of the receptor, in a saturable fashion., This association is specific for CCK-8; no association was observed upon, titration of CCK(A)-R(1-47) with other peptide hormones. The, ligand/receptor complex was characterized by intermolecular NOEs between, Tyr(27) and Met(28) of CCK-8 and W39 of CCK(A)-R(1-47). These findings, suggest that CCK-8 binds to CCK(A) with the C-terminus within the, seven-helical bundle and the N-terminus of the ligand, projecting out, between TM1 and TM7, forming specific interactions with the N-terminus of, the CCK(A) receptor. This mode of ligand binding, consistent with, published mutagenesis studies, requires variation of the interpretation of, recent findings from photoaffinity cross-linking studies.
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The bimolecular complex of the C-terminal octapeptide of cholecystokinin, CCK-8, with the N-terminus of the CCK(A)-receptor, CCK(A)-R(1-47), has been structurally characterized by high-resolution NMR and computational refinement. The conformation of CCK(A)-R(1-47), within the lipid environment used for the spectroscopic studies, consists of a well-defined alpha-helix (residues 3-9) followed by a beta-sheet stabilized by a disulfide linkage between C18 and C29, leading to the first transmembrane alpha-helix (TM1). Titration of CCK(A)-R(1-47) with CCK-8 specifically affects the NMR signals of W39 of the receptor, in a saturable fashion. This association is specific for CCK-8; no association was observed upon titration of CCK(A)-R(1-47) with other peptide hormones. The ligand/receptor complex was characterized by intermolecular NOEs between Tyr(27) and Met(28) of CCK-8 and W39 of CCK(A)-R(1-47). These findings suggest that CCK-8 binds to CCK(A) with the C-terminus within the seven-helical bundle and the N-terminus of the ligand, projecting out between TM1 and TM7, forming specific interactions with the N-terminus of the CCK(A) receptor. This mode of ligand binding, consistent with published mutagenesis studies, requires variation of the interpretation of recent findings from photoaffinity cross-linking studies.
==About this Structure==
==About this Structure==
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1D6G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with NH2 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1D6G OCA].
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1D6G is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=NH2:'>NH2</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D6G OCA].
==Reference==
==Reference==
Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy., Pellegrini M, Mierke DF, Biochemistry. 1999 Nov 9;38(45):14775-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10555959 10555959]
Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy., Pellegrini M, Mierke DF, Biochemistry. 1999 Nov 9;38(45):14775-83. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10555959 10555959]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Mierke, D.F.]]
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[[Category: Mierke, D F.]]
[[Category: Pellegrini, M.]]
[[Category: Pellegrini, M.]]
[[Category: NH2]]
[[Category: NH2]]
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[[Category: complex gpcr-ligand]]
[[Category: complex gpcr-ligand]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 16:29:37 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 12:13:27 2008''

Revision as of 10:13, 21 February 2008


1d6g

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MOLECULAR COMPLEX OF CHOLECYSTOKININ-8 AND N-TERMINUS OF THE CHOLECYSTOKININ A RECEPTOR BY NMR SPECTROSCOPY

Overview

The bimolecular complex of the C-terminal octapeptide of cholecystokinin, CCK-8, with the N-terminus of the CCK(A)-receptor, CCK(A)-R(1-47), has been structurally characterized by high-resolution NMR and computational refinement. The conformation of CCK(A)-R(1-47), within the lipid environment used for the spectroscopic studies, consists of a well-defined alpha-helix (residues 3-9) followed by a beta-sheet stabilized by a disulfide linkage between C18 and C29, leading to the first transmembrane alpha-helix (TM1). Titration of CCK(A)-R(1-47) with CCK-8 specifically affects the NMR signals of W39 of the receptor, in a saturable fashion. This association is specific for CCK-8; no association was observed upon titration of CCK(A)-R(1-47) with other peptide hormones. The ligand/receptor complex was characterized by intermolecular NOEs between Tyr(27) and Met(28) of CCK-8 and W39 of CCK(A)-R(1-47). These findings suggest that CCK-8 binds to CCK(A) with the C-terminus within the seven-helical bundle and the N-terminus of the ligand, projecting out between TM1 and TM7, forming specific interactions with the N-terminus of the CCK(A) receptor. This mode of ligand binding, consistent with published mutagenesis studies, requires variation of the interpretation of recent findings from photoaffinity cross-linking studies.

About this Structure

1D6G is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.

Reference

Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy., Pellegrini M, Mierke DF, Biochemistry. 1999 Nov 9;38(45):14775-83. PMID:10555959

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