PDBsum entry 4log

Transcription

PDB id: 4log

Contents

Protein chains

553 a.a.

232 a.a.

Waters ×62

PDB id:

4log

Name:

Transcription

Title:

The crystal structure of the orphan nuclear receptor pnr ligand binding domain fused with mbp

Structure:

Maltose abc transporter periplasmic protein and nr2e3 protein chimeric construct. Chain: a, b. Fragment: k0bgg6_eco1e unp residues 26-392. Q8ivz9_human unp residues 129-322. Engineered: yes

Source:

Escherichia coli o104:h4, homo sapiens. Organism_taxid: 1133853, 9606. Strain: k12 / dh10b. Gene: ecdh10b_4223, male, o3o_01660, nr2e3. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.70Å R-factor: 0.287 R-free: 0.307

Authors:

M.E.Tan,X.E.Zhou,F.-F.Soon,X.Li,J.Li,E.-L.Yong,K.Melcher,H.E.Xu

Key ref:

M.H.Tan et al. (2013). The crystal structure of the orphan nuclear receptor NR2E3/PNR ligand binding domain reveals a dimeric auto-repressed conformation. Plos One, 8, e74359. PubMed id: 24069298 DOI: 10.1371/journal.pone.0074359

Date:

12-Jul-13 Release date: 09-Oct-13

Protein chain

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 553 a.a.*

Protein chain

Q9Y5X4  (NR2E3_HUMAN) -  Photoreceptor-specific nuclear receptor from Homo sapiens

Seq: 410 a.a.

Struc: 553 a.a.*

Protein chain

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 232 a.a.*

Protein chain

Q9Y5X4  (NR2E3_HUMAN) -  Photoreceptor-specific nuclear receptor from Homo sapiens

Seq: 410 a.a.

Struc: 232 a.a.*

* PDB and UniProt seqs differ at 244 residue positions (black crosses)

Enzyme reactions

• Enzyme class: Chains A, B: E.C.?

DOI no: 10.1371/journal.pone.0074359

Plos One 8:e74359 (2013)

PubMed id: 24069298

The crystal structure of the orphan nuclear receptor NR2E3/PNR ligand binding domain reveals a dimeric auto-repressed conformation.

M.H.Tan, X.E.Zhou, F.F.Soon, X.Li, J.Li, E.L.Yong, K.Melcher, H.E.Xu.

ABSTRACT

Photoreceptor-specific nuclear receptor (PNR, NR2E3) is a key transcriptional regulator of human photoreceptor differentiation and maintenance. Mutations in the NR2E3-encoding gene cause various retinal degenerations, including Enhanced S-cone syndrome, retinitis pigmentosa, and Goldman-Favre disease. Although physiological ligands have not been identified, it is believed that binding of small molecule agonists, receptor desumoylation, and receptor heterodimerization may switch NR2E3 from a transcriptional repressor to an activator. While these features make NR2E3 a potential therapeutic target for the treatment of retinal diseases, there has been a clear lack of structural information for the receptor. Here, we report the crystal structure of the apo NR2E3 ligand binding domain (LBD) at 2.8 Å resolution. Apo NR2E3 functions as transcriptional repressor in cells and the structure of its LBD is in a dimeric auto-repressed conformation. In this conformation, the putative ligand binding pocket is filled with bulky hydrophobic residues and the activation-function-2 (AF2) helix occupies the canonical cofactor binding site. Mutations designed to disrupt either the AF2/cofactor-binding site interface or the dimer interface compromised the transcriptional repressor activity of this receptor. Together, these results reveal several conserved structural features shared by related orphan nuclear receptors, suggest that most disease-causing mutations affect the receptor's structural integrity, and allowed us to model a putative active conformation that can accommodate small ligands in its pocket.