title: General and specific determinants of the selective interactions between SRC-1 NR box-2 and target nuclear receptors.
abstract: Nuclear receptors (NRs) associate with various coactivator proteins via direct interaction with a short LXXLL motif (also called NR box) that is present among coactivators. Here we identified the critical residues within or outside NR box-2 or -3 of SRC-1, which are required for the optimal interaction with LXR/RXR heterodimers using the yeast one- plus two-hybrid screening system. The critical residues of NR box-2 were broadly located from position -4 to +5 of the NR box (where +1 is the first L of LXXLL motif), whereas those of NR box-3 were located between -1 and +5. We assessed the functional and physical interactions between the isolated NR box-2 mutants and various NRs. Among the NR box-2 mutants, H-3Q, I-1T/V and H+2P mutants evidenced different interaction profiles depending on the target NRs, thereby indicating that these residues are the specific determinants required for the selective interaction between the SRC-1 NR box-2 and a given receptor.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju, 500-757, South Korea.
authors.forename: You Lee
authors.initials: YL
authors.lastname: Son
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Park
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D005697:Galactosides; D057809:HEK293 Cells; D006801:Humans; D007211:Indoles; D000071518:Liver X Receptors; D016296:Mutagenesis; D056920:Nuclear Receptor Coactivator 1 / Q000235:genetics / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D054730:Protein Interaction Domains and Motifs / Q000235:genetics*; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D005697:Galactosides; D007211:Indoles; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D047488:Retinoid X Receptors; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; C044888:5-bromo-4-chloro-3-indolyl beta-galactoside