LIG_NRBOX

The NR (nuclear receptor) box allows for specific interaction with NRs and is primarily found in co-activators of NRs (Leo,2000). The consensus sequence of the NR box is LXXLL (Heery,1997). Several structures with NR box peptides bound to different NRs have been solved. The structures reveal that the NR box forms an alpha-helix that interacts with a hydrophobic groove in the AF-2 domain. The three leucines form a hydrophobic face that interacts with the AF-2 domain groove, and the helix is positioned by the so-called 'charge clamp', where a conserved glutamate and lysin residue forms hydrogen bonds with the backbone of the N- and C-terminal end of the helix respectively.
Several NR box containing proteins have more than one NR box, such as the steroid receptor co-activator (SRC) family of proteins which have three (TIF2/GRIP) or four (SRC-1). The structure of a 88 peptide from SRC-1, containing two NR boxes, bound to a dimer of the ligand binding domain of PPARgamma shows that each NR box binds to one monomer (Nolte,1998), suggesting that two NR boxes can work in consort. Variants of the LxxLL motif has been reported, but has not yet been incorporated into the ELM resource. The related Corepressor nuclear receptor box (LIG_CORNRBOX) mediates binding of co-repressors to nuclear receptors.