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Signature of the oligomeric behaviour of nuclear receptors at the sequence and structural level
Author(s) -
Brelivet Yann,
Kammerer Sabrina,
Rochel Natacha,
Poch Olivier,
Moras Dino
Publication year - 2004
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/sj.embor.7400119
Subject(s) - biology , nuclear receptor , transcription factor , genetics , retinoid x receptor , caenorhabditis elegans , mutagenesis , microbiology and biotechnology , gene , biochemistry , mutation
Nuclear receptors (NRs) are ligand‐dependent transcription factors that control a large number of physiological events through the regulation of gene transcription. NRs function either as homodimers or as heterodimers with retinoid X receptor/ultraspiracle protein (RXR/USP). A structure‐based sequence analysis aimed at discovering the molecular mechanism that controls the dimeric association of the ligand‐binding domain reveals two sets of differentially conserved residues, which partition the entire NR superfamily into two classes related to their oligomeric behaviour. Site‐directed mutagenesis confirms the functional importance of these residues for the dimerization process and/or transcriptional activity. All homodimers belong to class I, in which the related residues contribute a communication pathway of two salt bridges linking helix 1 on the cofactor‐binding site to the dimer interface. A salt bridge involving a differentially conserved arginine residue in loop H8–H9 defines the signature motif of heterodimers. RXR/USP and all Caenorhabditis elegans NRs belong to class I, supporting the hypothesis of an earlier emergence of this class.