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PDBsum entry 1dp4
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protein ligands metals Protein-protein interface(s) links
Hormone/growth factor receptor, lyase PDB id
1dp4

 

 

 

 

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JSmol PyMol  
Contents
Protein chains
425 a.a. *
Ligands
NAG-NAG ×4
SO4 ×9
NAG
Metals
_CL ×2
Waters ×514
* Residue conservation analysis
PDB id:
1dp4
Name: Hormone/growth factor receptor, lyase
Title: Dimerized hormone binding domain of the atrial natriuretic peptide receptor
Structure: Atrial natriuretic peptide receptor a. Chain: a, c. Fragment: hormone binding domain. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: chlorocebus aethiops. Expression_system_taxid: 9534.
Resolution:
2.00Å     R-factor:   0.198     R-free:   0.225
Authors: F.Van Den Akker,X.Zhang,M.Miyagi,X.Huo,K.S.Misono,V.C.Yee
Key ref:
F.van den Akker et al. (2000). Structure of the dimerized hormone-binding domain of a guanylyl-cyclase-coupled receptor. Nature, 406, 101-104. PubMed id: 10894551 DOI: 10.1038/35017602
Date:
23-Dec-99     Release date:   12-Jul-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
P18910  (ANPRA_RAT) -  Atrial natriuretic peptide receptor 1 from Rattus norvegicus
Seq:
Struc: 		 
Seq:
Struc: 		 
Seq:
Struc: 		1057 a.a.
425 a.a.
Key:    Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.4.6.1.2  - guanylate cyclase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: GTP = 3',5'-cyclic GMP + diphosphate
GTP
 =
3',5'-cyclic GMP
Bound ligand (Het Group name = NAG)
matches with 48.00% similarity 		+ diphosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site

 

 
    reference    
 
 
DOI no: 10.1038/35017602 Nature 406:101-104 (2000)
PubMed id: 10894551  
 
 
Structure of the dimerized hormone-binding domain of a guanylyl-cyclase-coupled receptor.
F.van den Akker, X.Zhang, M.Miyagi, X.Huo, K.S.Misono, V.C.Yee.
 
  ABSTRACT  
 
The atrial natriuretic peptide (ANP) hormone is secreted by the heart in response to an increase in blood pressure. ANP exhibits several potent anti-hypertensive actions in the kidney, adrenal gland and vascular system. These actions are induced by hormone binding extracellularly to the ANP receptor, thereby activating its intracellular guanylyl cyclase domain for the production of cyclic GMP. Here we present the crystal structure of the glycosylated dimerized hormone-binding domain of the ANP receptor at 2.0-A resolution. The monomer comprises two interconnected subdomains, each encompassing a central beta-sheet flanked by alpha-helices, and exhibits the type I periplasmic binding protein fold. Dimerization is mediated by the juxtaposition of four parallel helices, arranged two by two, which brings the two protruding carboxy termini into close relative proximity. From affinity labelling and mutagenesis studies, the ANP-binding site maps to the side of the dimer crevice and extends to near the dimer interface. A conserved chloride-binding site is located in the membrane distal domain, and we found that hormone binding is chloride dependent. These studies suggest mechanisms for hormone activation and the allostery of the ANP receptor.
 
  Selected figure(s)  
 
Figure 1.
Figure 1: Crystal structure of the ANP receptor hormone-binding domain dimer. a, Ribbon diagram showing disulphide bonds (red), glycosylation (purple ball-and-stick), disordered glycosylation sites (purple spheres) and bound chlorides (yellow). The extrapolated C terminus of the second monomer (blue) and two transmembrane helices are modelled. b, The ANP-binding site on the receptor, shown as a space-filling model. M173 and H195 (blue), E169 and H185 (red), H185 and A202 (green), and Y88 and Y120 are highlighted. Residues 98, 113, 115, 158, 166 and the common E169 (light brown, 115 is hidden from view) are structurally equivalent to AmiC residues that interact with AmiR6. The dark grey 262-269 loop reaches over from the second monomer and forms a concave surface at one edge of the binding site that may be involved in hormone interactions. c, As b, but rotated 85° about the horizontal axis. d, Electrostatic surface representation generated using GRASP29, with positive and negative charges in blue and red, respectively, and the putative effector pocket labelled 'E'. 		Figure 2.
Figure 2: The chloride-binding site in the ligand-binding domain of the ANP receptor. A 25-4-Å resolution anomalous difference Fourier electron density contoured at 5 is shown in blue.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2000, 406, 101-104) copyright 2000.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
  21375691 K.N.Pandey (2011).
The functional genomics of guanylyl cyclase/natriuretic peptide receptor-A: Perspectives and paradigms.
  FEBS J, 278, 1792-1807.  
  21375693 K.S.Misono, J.S.Philo, T.Arakawa, C.M.Ogata, Y.Qiu, H.Ogawa, and H.S.Young (2011).
Structure, signaling mechanism and regulation of the natriuretic peptide receptor guanylate cyclase.
  FEBS J, 278, 1818-1829.  
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.  
  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
19828552 R.B.Yang, H.K.Au, C.R.Tzeng, M.T.Tsai, P.Wu, Y.C.Wu, T.Y.Ling, and Y.H.Huang (2010).
Characterization of a novel cell-surface protein expressed on human sperm.
  Hum Reprod, 25, 42-51.  
20105301 X.Ma, A.Beuve, and F.van den Akker (2010).
Crystal structure of the signaling helix coiled-coil domain of the beta-1 subunit of the soluble guanylyl cyclase.
  BMC Struct Biol, 10, 2.
PDB code: 3hls
19523832 C.O.Ortiz, S.Faumont, J.Takayama, H.K.Ahmed, A.D.Goldsmith, R.Pocock, K.E.McCormick, H.Kunimoto, Y.Iino, S.Lockery, and O.Hobert (2009).
Lateralized gustatory behavior of C. elegans is controlled by specific receptor-type guanylyl cyclases.
  Curr Biol, 19, 996.  
19187227 H.Ogawa, Y.Qiu, L.Huang, S.W.Tam-Chang, H.S.Young, and K.S.Misono (2009).
Structure of the atrial natriuretic peptide receptor extracellular domain in the unbound and hormone-bound states by single-particle electron microscopy.
  FEBS J, 276, 1347-1355.  
19926516 J.Nickel, W.Sebald, J.C.Groppe, and T.D.Mueller (2009).
Intricacies of BMP receptor assembly.
  Cytokine Growth Factor Rev, 20, 367-377.  
19393286 P.Pattanaik, L.Fromondi, K.P.Ng, J.He, and F.van den Akker (2009).
Expression, purification, and characterization of the intra-cellular domain of the ANP receptor.
  Biochimie, 91, 888-893.  
19648115 S.Saha, K.H.Biswas, C.Kondapalli, N.Isloor, and S.S.Visweswariah (2009).
The linker region in receptor guanylyl cyclases is a key regulatory module: mutational analysis of guanylyl cyclase C.
  J Biol Chem, 284, 27135-27145.  
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.  
18412262 J.Vijayalakshmi, B.J.Akerley, and M.A.Saper (2008).
Structure of YraM, a protein essential for growth of Haemophilus influenzae.
  Proteins, 73, 204-217.
PDB code: 3ckm
19746200 K.N.Pandey (2008).
Emerging Roles of Natriuretic Peptides and their Receptors in Pathophysiology of Hypertension and Cardiovascular Regulation.
  J Am Soc Hypertens, 2, 210-226.  
18713751 M.Hartmann, B.V.Skryabin, T.Müller, A.Gazinski, J.Schröter, B.Gassner, V.O.Nikolaev, M.Bünemann, and M.Kuhn (2008).
Alternative splicing of the guanylyl cyclase-a receptor modulates atrial natriuretic Peptide signaling.
  J Biol Chem, 283, 28313-28320.  
18384890 V.V.Gurevich, and E.V.Gurevich (2008).
How and why do GPCRs dimerize?
  Trends Pharmacol Sci, 29, 234-240.  
18022808 C.Dissous, A.Ahier, and N.Khayath (2007).
Protein tyrosine kinases as new potential targets against human schistosomiasis.
  Bioessays, 29, 1281-1288.  
17429599 I.Pagel-Langenickel, J.Buttgereit, M.Bader, and T.H.Langenickel (2007).
Natriuretic peptide receptor B signaling in the cardiovascular system: protection from cardiac hypertrophy.
  J Mol Med, 85, 797-810.  
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
16448393 C.Moro, and M.Berlan (2006).
Cardiovascular and metabolic effects of natriuretic peptides.
  Fundam Clin Pharmacol, 20, 41-49.  
16547101 C.O.Ortiz, J.F.Etchberger, S.L.Posy, C.Frøkjaer-Jensen, S.Lockery, B.Honig, and O.Hobert (2006).
Searching for neuronal left/right asymmetry: genomewide analysis of nematode receptor-type guanylyl cyclases.
  Genetics, 173, 131-149.  
16902599 Y.Fortin, and A.De Léan (2006).
Role of cyclic GMP and calcineurin in homologous and heterologous desensitization of natriuretic peptide receptor-A.
  Can J Physiol Pharmacol, 84, 539-546.  
16284729 M.Hasegawa, Y.Matsumoto-Ishikawa, A.Hijikata, Y.Hidaka, M.Go, and Y.Shimonishi (2005).
Disulfide linkages and a three-dimensional structure model of the extracellular ligand-binding domain of guanylyl cyclase C.
  Protein J, 24, 315-325.  
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.  
15758553 T.Nakayama (2005).
The genetic contribution of the natriuretic peptide system to cardiovascular diseases.
  Endocr J, 52, 11-21.  
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.  
15117952 H.Ogawa, Y.Qiu, C.M.Ogata, and K.S.Misono (2004).
Crystal structure of hormone-bound atrial natriuretic peptide receptor extracellular domain: rotation mechanism for transmembrane signal transduction.
  J Biol Chem, 279, 28625-28631.
PDB code: 1t34
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.  
14600147 Y.Qiu, H.Ogawa, M.Miyagi, and K.S.Misono (2004).
Constitutive activation and uncoupling of the atrial natriuretic peptide receptor by mutations at the dimer interface. Role of the dimer structure in signalling.
  J Biol Chem, 279, 6115-6123.  
12547834 A.De Léan, N.McNicoll, and J.Labrecque (2003).
Natriuretic peptide receptor A activation stabilizes a membrane-distal dimer interface.
  J Biol Chem, 278, 11159-11166.  
12850210 H.Jingami, S.Nakanishi, and K.Morikawa (2003).
Structure of the metabotropic glutamate receptor.
  Curr Opin Neurobiol, 13, 271-278.  
14501129 H.Ogawa, X.Zhang, Y.Qiu, C.M.Ogata, and K.S.Misono (2003).
Crystallization and preliminary X-ray analysis of the atrial natriuretic peptide (ANP) receptor extracellular domain complex with ANP: use of ammonium sulfate as the cryosalt.
  Acta Crystallogr D Biol Crystallogr, 59, 1831-1833.  
  14739996 I.Sokal, A.Alekseev, and K.Palczewski (2003).
Photoreceptor guanylate cyclase variants: cGMP production under control.
  Acta Biochim Pol, 50, 1075-1095.  
11772023 I.Sokal, A.Alekseev, W.Baehr, F.Haeseleer, and K.Palczewski (2002).
Soluble fusion proteins between single transmembrane photoreceptor guanylyl cyclases and their activators.
  Biochemistry, 41, 251-257.  
11704663 K.N.Pandey, H.T.Nguyen, G.D.Sharma, S.J.Shi, and A.M.Kriegel (2002).
Ligand-regulated internalization, trafficking, and down-regulation of guanylyl cyclase/atrial natriuretic peptide receptor-A in human embryonic kidney 293 cells.
  J Biol Chem, 277, 4618-4627.  
12135318 T.Nakayama, M.Soma, Y.Mizutani, X.Xinjuan, J.Honye, Y.Kaneko, D.Rahmutula, N.Aoi, K.Kosuge, S.Saito, Y.Ozawa, K.Kanmatsuse, and S.Kokubun (2002).
A novel missense mutation of exon 3 in the type A human natriuretic peptide receptor gene: possible association with essential hypertension.
  Hypertens Res, 25, 395-401.  
11558678 F.van den Akker (2001).
Detailed analysis of the atrial natriuretic factor receptor hormone-binding domain crystal structure.
  Can J Physiol Pharmacol, 79, 692-704.  
11522102 J.Mair, A.Hammerer-Lercher, and B.Puschendorf (2001).
The impact of cardiac natriuretic peptide determination on the diagnosis and management of heart failure.
  Clin Chem Lab Med, 39, 571-588.  
11558671 K.N.Pandey (2001).
Dynamics of internalization and sequestration of guanylyl cyclase/atrial natriuretic peptide receptor-A.
  Can J Physiol Pharmacol, 79, 631-639.  
11558677 R.K.Sharma, P.Yadav, and T.Duda (2001).
Allosteric regulatory step and configuration of the ATP-binding pocket in atrial natriuretic factor receptor guanylate cyclase transduction mechanism.
  Can J Physiol Pharmacol, 79, 682-691.  
11558675 S.Hirose, H.Hagiwara, and Y.Takei (2001).
Comparative molecular biology of natriuretic peptide receptors.
  Can J Physiol Pharmacol, 79, 665-672.  
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.

 

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