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PDBsum entry 1gea

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protein links
Neuropeptide PDB id
1gea
Jmol
Contents
Protein chain
21 a.a.
PDB id:
1gea
Name: Neuropeptide
Title: Receptor-bound conformation of pacap21
Structure: Pituitary adenylate cyclase activating polypeptide. Chain: a. Fragment: n-terminal domain(residue 132-152). Engineered: yes
Source: Synthetic: yes. Other_details: this sequence occurs naturally in humans.
NMR struc: 25 models
Authors: H.Inooka,T.Ohtaki,O.Kitahara,T.Ikegami,S.Endo,C.Kitada, K.Ogi,H.Onda,M.Fujino,M.Shirakawa
Key ref:
H.Inooka et al. (2001). Conformation of a peptide ligand bound to its G-protein coupled receptor. Nat Struct Biol, 8, 161-165. PubMed id: 11175907 DOI: 10.1038/84159
Date:
20-Oct-00     Release date:   20-Apr-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P18509  (PACA_HUMAN) -  Pituitary adenylate cyclase-activating polypeptide
Seq:
Struc:
176 a.a.
21 a.a.*
Key:    PfamA domain  Secondary structure
* PDB and UniProt seqs differ at 1 residue position (black cross)

 

 
DOI no: 10.1038/84159 Nat Struct Biol 8:161-165 (2001)
PubMed id: 11175907  
 
 
Conformation of a peptide ligand bound to its G-protein coupled receptor.
H.Inooka, T.Ohtaki, O.Kitahara, T.Ikegami, S.Endo, C.Kitada, K.Ogi, H.Onda, M.Fujino, M.Shirakawa.
 
  ABSTRACT  
 
Many peptide hormones elicit a wide array of physiological effects by binding to G-protein coupled receptors. We have determined the conformation of pituitary adenylate cyclase activating polypeptide, PACAP(1--21)NH(2), bound to a PACAP-specific receptor by NMR spectroscopy. Residues 3--7 form a unique beta-coil structure that is preceded by an N-terminal extended tail. This beta-coil creates a patch of hydrophobic residues that is important for receptor binding. In contrast, the C-terminal region (residues 8--21) forms an alpha-helix, similar to that in the micelle-bound PACAP. Thus, the conformational difference between PACAP in the receptor-bound and the micelle-bound states is limited to the N-terminal seven residues. This observation is consistent with the two-step ligand transportation model in which PACAP first binds to the membrane nonspecifically and then diffuses two-dimensionally in search of its receptor; a conformational change at the N-terminal region then allows specific interactions between the ligand and the receptor.
 
  Selected figure(s)  
 
Figure 3.
Figure 3. Stereo views of the PACAP peptides. Superpositions of the heavy atoms of 25 NMR derived structures of a, receptor-bound PACAP21 and b, micelle-bound PACAP27. In the structure of micelle-bound PACAP27, the side chain heavy atoms in the nonconverged region (residues 1 -4) do not superimpose.
Figure 4.
Figure 4. The N-terminal -coil structure of the receptor-bound PACAP21. a, Superimposition of the receptor-bound PACAP21 (red) and the micelle-bound PACAP27 (green). Side chains of Ile 5, Phe 6, Tyr 10 and Arg 14 are indicated as ball-and-stick models. b, Closeup view of the N-terminal -coil structure in stick representation (left) and showing the solvent accessible surface (right). The hydrophobic residues Ile 5, Phe 6 and Tyr 10 are shown in yellow, Gly 4 is in red, and Arg 14 in cyan. c, Schematic of the two-step ligand transportation model for PACAP. The peptide binds nonspecifically to cell membranes, forming an -helix at the C-terminal region, and then undergoes two-dimensional diffusion to the receptor where the formation of the N-terminal -coil is induced upon binding.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 161-165) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21294225 A.Santoprete, E.Capitò, P.E.Carrington, A.Pocai, M.Finotto, A.Langella, P.Ingallinella, K.Zytko, S.Bufali, S.Cianetti, M.Veneziano, F.Bonelli, L.Zhu, E.Monteagudo, D.J.Marsh, R.Sinharoy, E.Bianchi, and A.Pessi (2011).
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Crystal structure of glucagon-like peptide-1 in complex with the extracellular domain of the glucagon-like peptide-1 receptor.
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PDB code: 3iol
20453923 D.N.Langelaan, and J.K.Rainey (2010).
Membrane catalysis of peptide-receptor binding.
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20939117 M.X.Wei, P.Hu, P.Wang, S.Naruse, K.Nokihara, V.Wray, and T.Ozaki (2010).
Possible key residues that determine left gastric artery blood flow response to PACAP in dogs.
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Passing the baton in class B GPCRs: peptide hormone activation via helix induction?
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VPAC and PAC receptors: From ligands to function.
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PDB code: 2qkh
17360332 C.R.Grace, M.H.Perrin, J.Gulyas, M.R.Digruccio, J.P.Cantle, J.E.Rivier, W.W.Vale, and R.Riek (2007).
Structure of the N-terminal domain of a type B1 G protein-coupled receptor in complex with a peptide ligand.
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PDB codes: 2jnc 2jnd
17470806 C.Sun, D.Song, R.A.Davis-Taber, L.W.Barrett, V.E.Scott, P.L.Richardson, A.Pereda-Lopez, M.E.Uchic, L.R.Solomon, M.R.Lake, K.A.Walter, P.J.Hajduk, and E.T.Olejniczak (2007).
Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS.
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PDB code: 2jod
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PDB code: 2obu
17541576 M.Baldus (2007).
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17192263 M.F.Mesleh, W.A.Shirley, C.E.Heise, N.Ling, R.A.Maki, and R.P.Laura (2007).
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PDB code: 2o8z
16826539 C.R.Sanders, and F.Sönnichsen (2006).
Solution NMR of membrane proteins: practice and challenges.
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16997863 D.A.Keire, M.Kumar, W.Hu, J.Sinnett-Smith, and E.Rozengurt (2006).
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16773462 R.Sankararamakrishnan (2006).
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Are hormones from the neuropeptide Y family recognized by their receptors from the membrane-bound state?
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  Arch Pharm (Weinheim), 338, 217-228.  
16169979 T.Nakamura, H.Takahashi, K.Takeuchi, T.Kohno, K.Wakamatsu, and I.Shimada (2005).
Direct determination of a membrane-peptide interface using the nuclear magnetic resonance cross-saturation method.
  Biophys J, 89, 4051-4055.  
15964843 X.Tian, J.Guo, F.Yao, D.P.Yang, and A.Makriyannis (2005).
The conformation, location, and dynamic properties of the endocannabinoid ligand anandamide in a membrane bilayer.
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12960362 S.Luca, J.F.White, A.K.Sohal, D.V.Filippov, J.H.van Boom, R.Grisshammer, and M.Baldus (2003).
The conformation of neurotensin bound to its G protein-coupled receptor.
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12724331 S.Runge, C.Gram, H.Brauner-Osborne, K.Madsen, L.B.Knudsen, and B.S.Wulff (2003).
Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus.
  J Biol Chem, 278, 28005-28010.  
12056543 C.Giragossian, M.Pellegrini, and D.F.Mierke (2002).
NMR studies of CCK-8/CCK1 complex support membrane-associated pathway for ligand-receptor interaction.
  Can J Physiol Pharmacol, 80, 383-387.  
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Structural characterization of the PIT-1/ETS-1 interaction: PIT-1 phosphorylation regulates PIT-1/ETS-1 binding.
  Proc Natl Acad Sci U S A, 99, 12657-12662.  
12080067 M.Shimada, X.Chen, T.Cvrk, H.Hilfiker, M.Parfenova, and G.V.Segre (2002).
Purification and characterization of a receptor for human parathyroid hormone and parathyroid hormone-related peptide.
  J Biol Chem, 277, 31774-31780.  
11965396 M.van Dongen, J.Weigelt, J.Uppenberg, J.Schultz, and M.Wikström (2002).
Structure-based screening and design in drug discovery.
  Drug Discov Today, 7, 471-478.  
11891118 T.P.Sakmar (2002).
Structure of rhodopsin and the superfamily of seven-helical receptors: the same and not the same.
  Curr Opin Cell Biol, 14, 189-195.  
11579442 D.F.Mierke, and C.Giragossian (2001).
Peptide hormone binding to G-protein-coupled receptors: structural characterization via NMR techniques.
  Med Res Rev, 21, 450-471.  
11358518 S.Sagan, O.Lequin, F.Frank, O.Convert, M.Ayoub, S.Lavielle, and G.Chassaing (2001).
Calpha methylation in molecular recognition. Application to substance P and the two neurokinin-1 receptor binding sites.
  Eur J Biochem, 268, 2997-3005.  
11397646 T.J.Gardella, and H.Jüppner (2001).
Molecular properties of the PTH/PTHrP receptor.
  Trends Endocrinol Metab, 12, 210-217.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.