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PDBsum entry 1jdp

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protein ligands metals Protein-protein interface(s) links
Signaling protein PDB id
1jdp
Jmol
Contents
Protein chains
396 a.a. *
18 a.a. *
Ligands
NDG ×2
NAG-NAG
NAG
Metals
_CL ×2
Waters ×470
* Residue conservation analysis
PDB id:
1jdp
Name: Signaling protein
Title: Crystal structure of hormone/receptor complex
Structure: Atrial natriuretic peptide clearance receptor. Chain: a, b. Synonym: npr-c. Engineered: yes. C-type natriuretic peptide. Chain: h. Synonym: cnp. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: drosophila. Expression_system_taxid: 7215. Expression_system_taxid: 7215
Biol. unit: Trimer (from PQS)
Resolution:
2.00Å     R-factor:   0.227     R-free:   0.248
Authors: X.-L.He,D.-C.Chow,M.M.Martick,K.C.Garcia
Key ref:
He Xl et al. (2001). Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone. Science, 293, 1657-1662. PubMed id: 11533490 DOI: 10.1126/science.1062246
Date:
14-Jun-01     Release date:   05-Sep-01    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P17342  (ANPRC_HUMAN) -  Atrial natriuretic peptide receptor 3
Seq:
Struc:
 
Seq:
Struc:
541 a.a.
396 a.a.
Protein chain
Pfam   ArchSchema ?
P23582  (ANFC_HUMAN) -  C-type natriuretic peptide
Seq:
Struc:
126 a.a.
18 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   2 terms 
  Biochemical function     hormone activity     1 term  

 

 
DOI no: 10.1126/science.1062246 Science 293:1657-1662 (2001)
PubMed id: 11533490  
 
 
Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone.
He Xl, Chow Dc, M.M.Martick, K.C.Garcia.
 
  ABSTRACT  
 
Natriuretic peptides (NPs) are vasoactive cyclic-peptide hormones important in blood pressure regulation through interaction with natriuretic cell-surface receptors. We report the hormone-binding thermodynamics and crystal structures at 2.9 and 2.0 angstroms, respectively, of the extracellular domain of the unliganded human NP receptor (NPR-C) and its complex with CNP, a 22-amino acid NP. A single CNP molecule is bound in the interface of an NPR-C dimer, resulting in asymmetric interactions between the hormone and the symmetrically related receptors. Hormone binding induces a 20 angstrom closure between the membrane-proximal domains of the dimer. In each monomer, the opening of an interdomain cleft, which is tethered together by a linker peptide acting as a molecular spring, is likely a conserved allosteric trigger for intracellular signaling by the natriuretic receptor family.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Conformational changes in the NPR-C complex and the molecular spring. (A) Backbone representations of bound (cyan) versus unliganded (purple) NPR-C (the peptide in the middle is shown in red). At the base of the structures, the width of the gap separating the COOH-terminal domains of the dimer in bound versus free form is indicated. The identical amino acid closest to the COOH-terminal at the base of the gap (Ala^208) was used in both structures as the point from which to measure the gap to the dimeric-related residue (Ala^208*). For the elbow angle of the structures, identical reference points (a vector defining an helix in the membrane-distal and -proximal domains) were chosen in bound versus free structures from which to measure an interdomain angle. (B) The spring tethering the membrane-distal and -proximal domains in each monomer is stretched and lengthened by 2.5 Å in the bound structure (40). A ribbon representation is shown of the linker peptide, along with the secondary structure elements leading up to and away from the peptide. The loose structure of the unbound peptide is obvious as compared with the straightened peptide in the complex. (C) The N-linked glycan at Asp248 forms extensive interactions with the linker peptide, which are broken upon hormone binding and conformational change (40). A stick representation of the peptide, the N-linked glycan, and the surrounding amino acids is shown. We have superimposed the Fo-Fc SIGMAA-weighted omit maps, at 2.9 Å (left) and 2.0 Å (right) of the NH[2]-linked glycan, to demonstrate the clarity of the carbohydrate conformational change.
Figure 4.
Fig. 4. Asymmetry of the hormone/receptor interfaces and the conformation of CNP. (A) Stick representation of the bound CNP peptide (orange) and the interacting amino acids from each NPR-C monomer (cyan and green) (40). The yellow spheres represent the bound chloride ions in each monomer. Ile^188, which has been shown to modulate the ligand pharmacology of NPR-C (37), is next to the CNP residue Phe^7, and is labeled in black. (B) This interface is then shown in an "open-book" view of the molecular surface of each receptor monomer. The CNP peptide is shown as a yellow backbone-and-stick model projected onto the respective buried surfaces (red patches) of each NPR-C monomer. The figures were drawn with BOBSCRIPT, RASTER3D, and VMD (41).
 
  The above figures are reprinted by permission from the AAAs: Science (2001, 293, 1657-1662) copyright 2001.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21317871 M.Sukumaran, M.Rossmann, I.Shrivastava, A.Dutta, I.Bahar, and I.H.Greger (2011).
Dynamics and allosteric potential of the AMPA receptor N-terminal domain.
  EMBO J, 30, 972-982.
PDB codes: 3o21 3p3w
20713070 P.Rondard, C.Goudet, J.Kniazeff, J.P.Pin, and L.Prézeau (2011).
The complexity of their activation mechanism opens new possibilities for the modulation of mGlu and GABAB class C G protein-coupled receptors.
  Neuropharmacology, 60, 82-92.  
20628403 S.Ito, S.Ohtsuki, Y.Katsukura, M.Funaki, Y.Koitabashi, A.Sugino, S.Murata, and T.Terasaki (2011).
Atrial natriuretic peptide is eliminated from the brain by natriuretic peptide receptor-C-mediated brain-to-blood efflux transport at the blood-brain barrier.
  J Cereb Blood Flow Metab, 31, 457-466.  
  20066666 H.Ogawa, Y.Qiu, J.S.Philo, T.Arakawa, C.M.Ogata, and K.S.Misono (2010).
Reversibly bound chloride in the atrial natriuretic peptide receptor hormone-binding domain: possible allosteric regulation and a conserved structural motif for the chloride-binding site.
  Protein Sci, 19, 544-557.
PDB code: 3a3k
20225302 N.Shaikh, L.Russo, E.Papaleo, P.Giannoni, L.De Gioia, F.Nicotra, R.Quarto, and L.Cipolla (2010).
C-type natriuretic peptide: Structural studies, fragment synthesis, and preliminary biological evaluation in human osteosarcoma cell lines.
  Biopolymers, 94, 213-219.  
19461966 A.Ahier, P.Rondard, N.Gouignard, N.Khayath, S.Huang, J.Trolet, D.J.Donoghue, M.Gauthier, J.P.Pin, and C.Dissous (2009).
A new family of receptor tyrosine kinases with a venus flytrap binding domain in insects and other invertebrates activated by aminoacids.
  PLoS One, 4, e5651.  
19274732 K.L.Longenecker, Q.Ruan, E.H.Fry, S.C.Saldana, S.E.Brophy, P.L.Richardson, and S.Y.Tetin (2009).
Crystal structure and thermodynamic analysis of diagnostic mAb 106.3 complexed with BNP 5-13 (C10A).
  Proteins, 76, 536-547.
PDB code: 3e8u
19461580 R.Jin, S.K.Singh, S.Gu, H.Furukawa, A.I.Sobolevsky, J.Zhou, Y.Jin, and E.Gouaux (2009).
Crystal structure and association behaviour of the GluR2 amino-terminal domain.
  EMBO J, 28, 1812-1823.
PDB codes: 3h5v 3h5w
18987130 T.Lauber, N.Tidten, I.Matecko, M.Zeeb, P.Rösch, and U.C.Marx (2009).
Design and characterization of a soluble fragment of the extracellular ligand-binding domain of the peptide hormone receptor guanylyl cyclase-C.
  Protein Eng Des Sel, 22, 1-7.  
19615076 X.Wang, W.Xu, X.Kong, D.Chen, G.Hellermann, T.A.Ahlert, J.D.Giaimo, S.A.Cormier, X.Li, R.F.Lockey, S.Mohapatra, and S.S.Mohapatra (2009).
Modulation of lung inflammation by vessel dilator in a mouse model of allergic asthma.
  Respir Res, 10, 66.  
17680687 M.Brylinski, and J.Skolnick (2008).
What is the relationship between the global structures of apo and holo proteins?
  Proteins, 70, 363-377.  
18388862 P.Rondard, S.Huang, C.Monnier, H.Tu, B.Blanchard, N.Oueslati, F.Malhaire, Y.Li, E.Trinquet, G.Labesse, J.P.Pin, and J.Liu (2008).
Functioning of the dimeric GABA(B) receptor extracellular domain revealed by glycan wedge scanning.
  EMBO J, 27, 1321-1332.  
18596692 Y.Gong, P.Cao, H.J.Yu, and T.Jiang (2008).
Crystal structure of the neurotrophin-3 and p75NTR symmetrical complex.
  Nature, 454, 789-793.
PDB code: 3buk
17576674 J.Boudet, V.Duval, H.Van Melckebeke, M.Blackledge, A.Amoroso, B.Joris, and J.P.Simorre (2007).
Conformational and thermodynamic changes of the repressor/DNA operator complex upon monomerization shed new light on regulation mechanisms of bacterial resistance against beta-lactam antibiotics.
  Nucleic Acids Res, 35, 4384-4395.
PDB code: 2p7c
17849398 L.Marinelli, S.Cosconati, T.Steinbrecher, V.Limongelli, A.Bertamino, E.Novellino, and D.A.Case (2007).
Homology Modeling of NR2B Modulatory Domain of NMDA Receptor and Analysis of Ifenprodil Binding.
  ChemMedChem, 2, 1498-1510.  
17960150 M.E.Call, and K.W.Wucherpfennig (2007).
Common themes in the assembly and architecture of activating immune receptors.
  Nat Rev Immunol, 7, 841-850.  
17057343 B.Altermark, A.O.Smalås, N.P.Willassen, and R.Helland (2006).
The structure of Vibrio cholerae extracellular endonuclease I reveals the presence of a buried chloride ion.
  Acta Crystallogr D Biol Crystallogr, 62, 1387-1391.
PDB codes: 2g7e 2g7f
16410359 M.Tateyama, and Y.Kubo (2006).
Dual signaling is differentially activated by different active states of the metabotropic glutamate receptor 1alpha.
  Proc Natl Acad Sci U S A, 103, 1124-1128.  
16765900 X.Wang, R.H.Baloh, J.Milbrandt, and K.C.Garcia (2006).
Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors.
  Structure, 14, 1083-1092.
PDB codes: 2gh0 2gyr 2gyz
15749162 A.Ahluwalia, and A.J.Hobbs (2005).
Endothelium-derived C-type natriuretic peptide: more than just a hyperpolarizing factor.
  Trends Pharmacol Sci, 26, 162-167.  
15955055 J.P.Pin, J.Kniazeff, J.Liu, V.Binet, C.Goudet, P.Rondard, and L.Prézeau (2005).
Allosteric functioning of dimeric class C G-protein-coupled receptors.
  FEBS J, 272, 2947-2955.  
15771567 M.E.Call, and K.W.Wucherpfennig (2005).
The T cell receptor: critical role of the membrane environment in receptor assembly and function.
  Annu Rev Immunol, 23, 101-125.  
15705168 M.Hasegawa, and Y.Shimonishi (2005).
Recognition and signal transduction mechanism of Escherichia coli heat-stable enterotoxin and its receptor, guanylate cyclase C.
  J Pept Res, 65, 261-271.  
15146390 C.F.Bartels, H.Bükülmez, P.Padayatti, D.K.Rhee, C.van Ravenswaaij-Arts, R.M.Pauli, S.Mundlos, D.Chitayat, L.Y.Shih, L.I.Al-Gazali, S.Kant, T.Cole, J.Morton, V.Cormier-Daire, L.Faivre, M.Lees, J.Kirk, G.R.Mortier, J.Leroy, B.Zabel, C.A.Kim, Y.Crow, N.E.Braverman, F.van den Akker, and M.L.Warman (2004).
Mutations in the transmembrane natriuretic peptide receptor NPR-B impair skeletal growth and cause acromesomelic dysplasia, type Maroteaux.
  Am J Hum Genet, 75, 27-34.  
15235591 J.Kniazeff, A.S.Bessis, D.Maurel, H.Ansanay, L.Prézeau, and J.P.Pin (2004).
Closed state of both binding domains of homodimeric mGlu receptors is required for full activity.
  Nat Struct Mol Biol, 11, 706-713.  
15152191 M.E.Call, J.Pyrdol, and K.W.Wucherpfennig (2004).
Stoichiometry of the T-cell receptor-CD3 complex and key intermediates assembled in the endoplasmic reticulum.
  EMBO J, 23, 2348-2357.  
14718564 S.Saran, and P.Schaap (2004).
Adenylyl cyclase G is activated by an intramolecular osmosensor.
  Mol Biol Cell, 15, 1479-1486.  
12906822 A.Farooq, L.Zeng, K.S.Yan, K.S.Ravichandran, and M.M.Zhou (2003).
Coupling of folding and binding in the PTB domain of the signaling protein Shc.
  Structure, 11, 905-913.
PDB codes: 1n3h 1oy2
12604783 B.H.Luo, T.A.Springer, and J.Takagi (2003).
Stabilizing the open conformation of the integrin headpiece with a glycan wedge increases affinity for ligand.
  Proc Natl Acad Sci U S A, 100, 2403-2408.  
12850210 H.Jingami, S.Nakanishi, and K.Morikawa (2003).
Structure of the metabotropic glutamate receptor.
  Curr Opin Neurobiol, 13, 271-278.  
  14739996 I.Sokal, A.Alekseev, and K.Palczewski (2003).
Photoreceptor guanylate cyclase variants: cGMP production under control.
  Acta Biochim Pol, 50, 1075-1095.  
12782243 J.P.Pin, T.Galvez, and L.Prézeau (2003).
Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors.
  Pharmacol Ther, 98, 325-354.  
12893874 K.Inoue, K.Naruse, S.Yamagami, H.Mitani, N.Suzuki, and Y.Takei (2003).
Four functionally distinct C-type natriuretic peptides found in fish reveal evolutionary history of the natriuretic peptide system.
  Proc Natl Acad Sci U S A, 100, 10079-10084.  
12552127 S.D.Chauhan, H.Nilsson, A.Ahluwalia, and A.J.Hobbs (2003).
Release of C-type natriuretic peptide accounts for the biological activity of endothelium-derived hyperpolarizing factor.
  Proc Natl Acad Sci U S A, 100, 1426-1431.  
12151600 A.S.Bessis, P.Rondard, F.Gaven, I.Brabet, N.Triballeau, L.Prezeau, F.Acher, and J.P.Pin (2002).
Closure of the Venus flytrap module of mGlu8 receptor and the activation process: Insights from mutations converting antagonists into agonists.
  Proc Natl Acad Sci U S A, 99, 11097-11102.  
11839490 H.J.Dyson, and P.E.Wright (2002).
Coupling of folding and binding for unstructured proteins.
  Curr Opin Struct Biol, 12, 54-60.  
12176315 M.M.Davis (2002).
A new trigger for T cells.
  Cell, 110, 285-287.  
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 codes are shown on the right.