1D6G

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

Summary for 1D6G

• Entry DOI: 10.2210/pdb1d6g/pdb
• Descriptor: cholecystokinin type a receptor, cholecystokinin-8 (2 entities in total)
• Functional Keywords: alpha-helix, beta-sheet, complex gpcr-ligand, hormone-growth factor complex, hormone/growth factor
• Biological source: Homo sapiens (Human); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P32238
• Total number of polymer chains: 2
• Total formula weight: 6288.16

Authors

Pellegrini, M.,Mierke, D.F. (deposition date: 1999-10-13, release date: 1999-11-17, Last modification date: 2024-10-16)

Primary citation

Pellegrini, M.,Mierke, D.F.
Molecular complex of cholecystokinin-8 and N-terminus of the cholecystokinin A receptor by NMR spectroscopy.
Biochemistry, 38:14775-14783, 1999

PubMed Abstract: 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.

PubMed: 10555959
DOI: 10.1021/bi991272l

Experimental method

SOLUTION NMR