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PDBsum entry 3f7d

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Transcription PDB id
3f7d
Jmol
Contents
Protein chain
238 a.a. *
Ligands
PRO-SER-LEU-LEU-
LYS-LYS-LEU-LEU-
LEU-ALA
P42
Waters ×123
* Residue conservation analysis
PDB id:
3f7d
Name: Transcription
Title: Sf-1 lbd bound by phosphatidylcholine
Structure: Nuclear receptor sf-1. Chain: a. Fragment: unp residues 219-462. Synonym: steroidogenic factor-1, nuclear receptor subfamily a, member 1. Engineered: yes. Mutation: yes. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha.
Source: Mus musculus. Mouse. Organism_taxid: 10090. Gene: nr5a1, ftzf1, rp23-354g20.5-001. Expressed in: escherichia coli. Expression_system_taxid: 562. Synthetic: yes. Organism_taxid: 10090
Resolution:
2.20Å     R-factor:   0.182     R-free:   0.241
Authors: E.P.Sablin,R.J.Fletterick
Key ref: E.P.Sablin et al. (2009). Structure of SF-1 bound by different phospholipids: evidence for regulatory ligands. Mol Endocrinol, 23, 25-34. PubMed id: 18988706 DOI: 10.1210/me.2007-0508
Date:
07-Nov-08     Release date:   09-Dec-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P33242  (STF1_MOUSE) -  Steroidogenic factor 1
Seq:
Struc:
462 a.a.
238 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 5 residue positions (black crosses)

 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     4 terms  

 

 
DOI no: 10.1210/me.2007-0508 Mol Endocrinol 23:25-34 (2009)
PubMed id: 18988706  
 
 
Structure of SF-1 bound by different phospholipids: evidence for regulatory ligands.
E.P.Sablin, R.D.Blind, I.N.Krylova, J.G.Ingraham, F.Cai, J.D.Williams, R.J.Fletterick, H.A.Ingraham.
 
  ABSTRACT  
 
Despite the fact that many nuclear receptors are ligand dependent, the existence of obligate regulatory ligands is debated for some receptors, including steroidogenic factor 1 (SF-1). Although fortuitously bound bacterial phospholipids were discovered in the structures of the SF-1 ligand-binding domain (LBD), these lipids might serve merely as structural ligands. Thus, we examined whether exogenously added phospholipids would exchange for these bacterial lipids and bind to SF-1. Here, we report the first crystal structure of the SF-1 LBD bound by the exchanged phosphatidylcholine. Although the bound phosphatidylcholine phospholipid mimics the conformation of bound bacterial phosphoplipids, two surface loops, L2-3 and L11-12, surrounding the entrance to the pocket vary significantly between different SF-1 LBD structures. Based on this observation, we hypothesized that a bound ligand might control the conformations of loops L2-3 and L11-12, and that conserved residues in these dynamic loops could influence ligand binding and the receptor function. Consistent with this hypothesis, impaired phospholipid exchange and diminished transcriptional activity were observed for loop L11-12 SF-1 mutants and for the loop L2-3 human mutant R255L. The endocrine disease associated with this L2-3 mutation coupled with our cellular and biochemical data suggest that critical residues at the mouth of the ligand-binding pocket have evolved for efficient binding of phospholipid ligands and for achieving optimal SF-1 activity.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20887963 A.Bashamboo, B.Ferraz-de-Souza, D.Lourenço, L.Lin, N.J.Sebire, D.Montjean, J.Bignon-Topalovic, J.Mandelbaum, J.P.Siffroi, S.Christin-Maitre, U.Radhakrishna, H.Rouba, C.Ravel, J.Seeler, J.C.Achermann, and K.McElreavey (2010).
Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1.
  Am J Hum Genet, 87, 505-512.  
20889131 B.C.Mullaney, R.D.Blind, G.A.Lemieux, C.L.Perez, I.C.Elle, N.J.Faergeman, M.R.Van Gilst, H.A.Ingraham, and K.Ashrafi (2010).
Regulation of C. elegans fat uptake and storage by acyl-CoA synthase-3 is dependent on NR5A family nuclear hormone receptor nhr-25.
  Cell Metab, 12, 398-410.  
20882396 M.Cellanetti, V.Gunda, L.Wang, A.Macchiarulo, and R.Pellicciari (2010).
Insights into the binding mode and mechanism of action of some atypical retinoids as ligands of the small heterodimer partner (SHP).
  J Comput Aided Mol Des, 24, 943-956.  
20372994 S.Mukherjee, and S.Mani (2010).
Orphan nuclear receptors as targets for drug development.
  Pharm Res, 27, 1439-1468.  
19549922 B.C.Lin, M.Suzawa, R.D.Blind, S.C.Tobias, S.E.Bulun, T.S.Scanlan, and H.A.Ingraham (2009).
Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation.
  Cancer Res, 69, 5415-5423.  
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.