58 research outputs found
Tandem mass spectrometry of multiply phosphorylated forms of a ?histidine-tag? derived from a recombinant protein kinase expressed in bacteria
All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta
Retinoids regulate gene expression through binding to the nuclear retinoic acid receptors (RARs) and retinoid X receptors (RXRs). In contrast, no ligands for the retinoic acid receptor-related orphan receptors beta and gamma (ROR beta and gamma) have been identified, yet structural data and structure-function analyses indicate that ROR beta is a ligand-regulated nuclear receptor. Using nondenaturing mass spectrometry and scintillation proximity assays we found that all-trans retinoic acid (ATRA) and several retinoids bind to the ROR beta ligand-binding domain (LBD). The crystal structures of the complex with ATRA and with the synthetic analog ALRT 1550 reveal the binding modes of these ligands. ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional activity suggesting that high-affinity, subtype-specific ligands could be designed for the identification of ROR beta target genes. Our results identify ROR beta as a retinoid-regulated nuclear receptor, providing a novel pathway for retinoid action
Examination of nuclear receptor expression in osteoblasts reveals rorβ as an important regulator of osteogenesis
Oligomerization behavior of the archaeal Sm2-type protein from Archaeoglobus fulgidus
As part of a functional analysis of archaeal Sm-related proteins, we have studied the oligomerization behavior of the Sm-2 type protein from the euryarchaeon Archaeoglobus fulgidus using gel filtration chromatography and noncovalent mass spectrometry. Our experiments show that the oligomeric state of the protein depends on the pH and presence of RNA. The protein forms a hexamer at acidic pH in the absence of RNA. The addition of RNA (oligo U10) induces the formation of a heptamer over the whole pH range studied. The stability of both the hexamer and the RNA-bound heptamer increases at lower pH
Ternary complex of human RORγ ligand-binding domain, inverse agonist and SMRT peptide shows a unique mechanism of corepressor recruitment
Specificity of receptor-ligand interactions and their effect on dimerisation as observed by electrospray mass spectrometry: bile acids form stable adducts to the RXRα
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