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PDBsum entry 1y9r

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Transcription, ligand binding protein PDB id
1y9r
Jmol
Contents
Protein chains
239 a.a. *
Ligands
1CA ×2
Waters ×461
* Residue conservation analysis
PDB id:
1y9r
Name: Transcription, ligand binding protein
Title: Crystal structure of the human mineralocorticoid receptor ligand-binding domain bound to deoxycorticosterone and harboring the s810l mutation responsible for a severe form of hypertension
Structure: Mineralocorticoid receptor. Chain: a, b. Fragment: ligand-binding domain. Synonym: mr. Nuclear receptor subfamily 3, group c, member 2. Engineered: yes. Mutation: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: uv20hl21-27. Gene: nr3c2, mcr, mlr. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
1.96Å     R-factor:   0.229     R-free:   0.267
Authors: J.Fagart,J.Huyet,G.M.Pinon,M.Rochel,C.Mayer,M.E.Rafestin- Oblin
Key ref:
J.Fagart et al. (2005). Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension. Nat Struct Mol Biol, 12, 554-555. PubMed id: 15908963 DOI: 10.1038/nsmb939
Date:
16-Dec-04     Release date:   24-May-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P08235  (MCR_HUMAN) -  Mineralocorticoid receptor
Seq:
Struc:
 
Seq:
Struc:
984 a.a.
239 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     nucleus   1 term 
  Biological process     steroid hormone mediated signaling pathway   2 terms 
  Biochemical function     DNA binding     3 terms  

 

 
DOI no: 10.1038/nsmb939 Nat Struct Mol Biol 12:554-555 (2005)
PubMed id: 15908963  
 
 
Crystal structure of a mutant mineralocorticoid receptor responsible for hypertension.
J.Fagart, J.Huyet, G.M.Pinon, M.Rochel, C.Mayer, M.E.Rafestin-Oblin.
 
  ABSTRACT  
 
The S810L mutation within the human mineralocorticoid receptor (MR S810L) induces severe hypertension and switches progesterone from antagonist to agonist. Here we report the crystal structures of the ligand-binding domain of MR S810L in complex with progesterone and deoxycorticosterone, an agonist of both wild-type and mutant MRs. These structures, the first for MR, identify the specific contacts created by Leu810 and clarify the mechanism of activation of MR S810L.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Crystal structures of the LBD of MR S810L. (a) Diagram showing LBD-DOC interactions. Hydrogen bonds and van der Waals interactions are solid arrows and dashed lines, respectively. The colors of the residue names are based on the LBD structural elements from which they originate. W indicates a water molecule. (b) Stereo view showing the superimposition of the ligand-binding pockets of MR S810L associated with DOC and with progesterone. The carbon atoms are light blue and white in the DOC -MR S810L and progesterone -MR S810L complexes, respectively. Only polar and charged residues, and two critical hydrophobic residues, are shown. This panel was produced using DINO (http://www.dino3d.org).
Figure 2.
Figure 2. Transcriptional activation of luciferase activity by mutant MRs in response to aldosterone and progesterone. (a,b) Transfected HEK-293T cells were exposed for 24 h to increasing concentrations of aldosterone (a, full lines), progesterone alone (a, dashed dotted) or 10^-7 M aldosterone plus increasing concentrations of progesterone (b). Transactivations were determined by luciferase activity, normalized to the internal -galactosidase control, and expressed as a percentage of the MR S810L activity at 10^-6 M aldosterone. Each point is the mean s.e.m. of three separate experiments.
 
  The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Mol Biol (2005, 12, 554-555) copyright 2005.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20333619 A.S.Veleiro, L.D.Alvarez, S.L.Eduardo, and G.Burton (2010).
Structure of the glucocorticoid receptor, a flexible protein that can adapt to different ligands.
  ChemMedChem, 5, 649-659.  
20723571 L.Jin, and Y.Li (2010).
Structural and functional insights into nuclear receptor signaling.
  Adv Drug Deliv Rev, 62, 1218-1226.  
19925636 N.Farman, E.Maubec, B.Poeggeler, J.E.Klatte, F.Jaisser, and R.Paus (2010).
The mineralocorticoid receptor as a novel player in skin biology: beyond the renal horizon?
  Exp Dermatol, 19, 100-107.  
20148675 P.Huang, V.Chandra, and F.Rastinejad (2010).
Structural overview of the nuclear receptor superfamily: insights into physiology and therapeutics.
  Annu Rev Physiol, 72, 247-272.  
19114086 C.D.Clyne, C.Y.Chang, R.Safi, P.J.Fuller, D.P.McDonnell, and M.J.Young (2009).
Purification and characterization of recombinant human mineralocorticoid receptor.
  Mol Cell Endocrinol, 302, 81-85.  
19325532 F.Martinez, M.L.Mansego, J.C.Escudero, J.Redon, and F.J.Chaves (2009).
Association of a mineralocorticoid receptor gene polymorphism with hypertension in a Spanish population.
  Am J Hypertens, 22, 649-655.  
19557178 M.E.Baker, D.J.Chang, and C.Chandsawangbhuwana (2009).
3D model of lamprey estrogen receptor with estradiol and 15alpha-hydroxy-estradiol.
  PLoS One, 4, e6038.  
18502379 J.Zhang, and D.S.Geller (2008).
Helix 3-helix 5 interactions in steroid hormone receptor function.
  J Steroid Biochem Mol Biol, 109, 279-285.  
16972228 L.Pujo, J.Fagart, F.Gary, D.T.Papadimitriou, A.Claës, X.Jeunemaître, and M.C.Zennaro (2007).
Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism.
  Hum Mutat, 28, 33-40.  
17306029 M.E.Baker, C.Chandsawangbhuwana, and N.Ollikainen (2007).
Structural analysis of the evolution of steroid specificity in the mineralocorticoid and glucocorticoid receptors.
  BMC Evol Biol, 7, 24.  
18174920 S.Viengchareun, D.Le Menuet, L.Martinerie, M.Munier, L.Pascual-Le Tallec, and M.Lombès (2007).
The mineralocorticoid receptor: insights into its molecular and (patho)physiological biology.
  Nucl Recept Signal, 5, e012.  
16601189 J.T.Bridgham, S.M.Carroll, and J.W.Thornton (2006).
Evolution of hormone-receptor complexity by molecular exploitation.
  Science, 312, 97.  
16503757 P.Fuller (2006).
The aldosterone receptor--new insights?
  Expert Opin Investig Drugs, 15, 201-203.  
16361444 H.Karst, S.Berger, M.Turiault, F.Tronche, G.Schütz, and M.Joëls (2005).
Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone.
  Proc Natl Acad Sci U S A, 102, 19204-19207.  
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.