Abstract

The NR (nuclear receptor) box allows for specific interaction with NRs and is primarily found in co-activators of NRs. The consensus sequence of the NR box is LXXLL (PMID: 9192902). 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 (PMID: 9744270), 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.

Recent review: PMID:10713439.
Related functional site: Corepressor nuclear receptor box (LIG_CORNRBOX).

 Selected references

 This ELM has been assigned the following Gene Ontology (GO) terms for biological process, cellular component and molecular function.

Biological Process
positive regulation of transcription	GO:0045941
regulation of transcription	GO:0045449
Cellular Component
nucleus	GO:0005634
Molecular Function
transcription factor binding	GO:0008134
transcription cofactor	GO:0003712
transcription co-activator	GO:0003713