1PK5

Crystal structure of the orphan nuclear receptor LRH-1

Summary for 1PK5

• Entry DOI: 10.2210/pdb1pk5/pdb
• Descriptor: Orphan nuclear receptor NR5A2 (2 entities in total)
• Functional Keywords: nuclear receptor, ligand-binding domain, lrh-1, gene regulation
• Biological source: Mus musculus (house mouse)
• Cellular location: Nucleus (Probable): P45448
• Total number of polymer chains: 2
• Total formula weight: 57463.94

Authors

Sablin, E.P.,Krylova, I.N.,Fletterick, R.J.,Ingraham, H.A. (deposition date: 2003-06-04, release date: 2003-07-01, Last modification date: 2023-08-16)

Primary citation

Sablin, E.P.,Krylova, I.N.,Fletterick, R.J.,Ingraham, H.A.
Structural basis for ligand-independent activation of the orphan nuclear receptor LRH-1
Mol.Cell, 11:1575-1585, 2003

PubMed Abstract: The orphan nuclear receptors SF-1 and LRH-1 are constitutively active, but it remains uncertain whether their activation is hormone dependent. We report the crystal structure of the LRH-1 ligand binding domain to 2.4 A resolution and find the receptor to be a monomer that adopts an active conformation with a large but empty hydrophobic pocket. Adding bulky side chains into this pocket resulted in full or greater activity suggesting that, while LRH-1 could accommodate potential ligands, these are dispensable for basal activity. Constitutive LRH-1 activity appears to be conferred by a distinct structural element consisting of an extended helix 2 that provides an additional layer to the canonical LBD fold. Mutating the conserved arginine in helix 2 reduced LRH-1 receptor activity and coregulator recruitment, consistent with the partial loss-of-function phenotype exhibited by an analogous SF-1 human mutant. These findings illustrate an alternative structural strategy for nuclear receptor stabilization in the absence of ligand binding.

PubMed: 12820970
DOI: 10.1016/S1097-2765(03)00236-3

Experimental method

X-RAY DIFFRACTION (2.4 Å)