Crystal structure of human nuclear receptor sf-1 (nr5a1) bound to pip2 at 2.8 a resolution

Joint Center for Structural Genomics (JCSG)

Partnership for Stem Cell Biology (STEMCELL)

(2S)-3-{[(R)-hydroxy{[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propane-1,2-diyl dihexadecanoate

The signaling phospholipid PIP3 creates a new interaction surface on the nuclear receptor SF-1.

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha

SMILES string: CCCCCCCCCCCCCCCC(=O)OCC(CO[P](O)(=O)OC1C(O)C(O)C (O[P](O)(O)=O)C(O[P](O)(O)=O)C1O)OC(=O)CCCCCCCCCCCCCCC

SF-1, STF-1, Adrenal 4-binding protein, Fushi tarazu factor homolog 1, Nuclear receptor subfamily 5 group A member 1, Steroid hormone receptor Ad4BP

PGC-1-alpha, PPAR-gamma coactivator 1-alpha, PPARGC-1-alpha, Ligand effect modulator 6

GSGGPNVPELILQLLQLEPDEDQVRARILGSLQEPTKSRPDQPAAFGLLCRMADQTFISIVDWARRCMVFKELEVADQMT
LLQNCWSELLVFDHIYRQVQHGKEGSILLVTGQEVELTTVATQAGSLLHSLVLRAQELVLQLLALQLDRQEFVCLKFIIL
FSLDLKFLNNHILVKDAQEKANAALLDYTLCHYPHSGDKFQQLLLCLVEVRALSMQAKEYLYHKHLGNEMPRNNLLIEML
QAKQT

SF-1, 6% PEG 8000, 0.2M MGOAC, 20% ETHYLENE GLYCOL, 0.067MM PIP2, 0.80MM 14-MER EEPSLLKKLLLAPA, NANODROP, VAPOR DIFFUSION, SITTING DROP, TEMPERATURE 277K

PGC-1ALPHA (PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA CO-ACTIVATOR-1ALPHA) PEPTIDE CONTAINING RESIDUES 139-EEPSLLKKLLLAPA-152

SF-1 (UNIPROT Q13285, NR5A1_HUMAN, STF1_HUMAN) LIGAND BINDING DOMAIN (LBD) WAS EXPRESSED WITH AN N-TERMINAL PURIFICATION TAG MGSDKIHHHHHHENLYFQG. THE TAG WAS REMOVED WITH TEV PROTEASE LEAVING ONLY A GLYCINE (0) FOLLOWED BY AMINO ACID RESIDUES 218-461 OF THE TARGET SEQUENCE. RESIDUES C247 AND C412 IN THIS SF-1 CONSTRUCT WERE MUTATED TO S247 AND S412. PEPTIDE CORRESPONDING TO THE PGC-1ALPHA (PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA CO-ACTIVATOR-1ALPHA) RESIDUES 139-EEPSLLKKLLLAPA-152 (UNIPROT Q9UBK2, PRGC1_HUMAN)WAS CO-CRYSTALLIZED WITH THE SF-1 LBD.

1. ATOM RECORD CONTAINS SUM OF TLS AND RESIDUAL B FACTORS. ANISOU RECORD CONTAINS SUM OF TLS AND RESIDUAL U FACTORS. 2. 1,2-ETHANEDIOL (EDO) FROM THE CRYSTALLIZATION SOLUTION HAS BEEN MODELED IN THE SOLVENT STRUCTURE. 3. PIP2 WAS CO-CRYSTALLIZED WITH THE SF-1 PROTEIN AND PGC-1ALPHA PEPTIDE.

NUCLEAR HORMONE RECEPTOR, NR5A1, SF-1 LIGAND BINDING DOMAIN, REGULATORY LIGANDS, TRANSCRIPTION, TRANSCRIPTION REGULATION, STRUCTURAL GENOMICS, JOINT CENTER FOR STRUCTURAL GENOMICS, JCSG, PROTEIN STRUCTURE INITIATIVE, PSI-BIOLOGY, PARTNERSHIP FOR STEM CELL BIOLOGY, PIP3, PIP2, NUCLEUS, NUCLEAR PHOSPHATIDYLINOSITOL PHOSPHATES, TRANSCRIPTION FACTOR-HORMONE complex, STEMCELL

SGGPNVPELILQLLQLEPDEDQVRARILGCLQEPTKSRPDQPAAFGLLCRMADQTFISIVDWARRCMVFKELEVADQMTL
LQNCWSELLVFDHIYRQVQHGKEGSILLVTGQEVELTTVATQAGSLLHSLVLRAQELVLQLLALQLDRQEFVCLKFIILF
SLDLKFLNNHILVKDAQEKANAALLDYTLCHYPHCGDKFQQLLLCLVEVRALSMQAKEYLYHKHLGNEMPRNNLLIEMLQ
AKQT