4nz6 | pdb_00004nz6
Steroid receptor RNA Activator (SRA) modification by the human Pseudouridine Synthase 1 (hPus1p): RNA binding, activity, and atomic model
Structural highlights
Disease[TRUA_HUMAN] Mitochondrial myopathy and sideroblastic anemia. Myopathy with lactic acidosis and sideroblastic anemia 1 (MLASA1) [MIM:600462]: A rare oxidative phosphorylation disorder specific to skeletal muscle and bone marrow. Affected individuals manifest progressive muscle weakness, exercise intolerance, lactic acidosis, sideroblastic anemia and delayed growth. Note=The disease is caused by mutations affecting the gene represented in this entry.[1] Function[TRUA_HUMAN] Converts specific uridines to PSI in a number of tRNA substrates. Acts on positions 27/28 in the anticodon stem and also positions 34 and 36 in the anticodon of an intron containing tRNA. Involved in regulation of nuclear receptor activity possibly through pseudouridylation of SRA1 RNA (By similarity). Publication Abstract from PubMedThe most abundant of the modified nucleosides, and once considered as the "fifth" nucleotide in RNA, is pseudouridine, which results from the action of pseudouridine synthases. Recently, the mammalian pseudouridine synthase 1 (hPus1p) has been reported to modulate class I and class II nuclear receptor responses through its ability to modify the Steroid receptor RNA Activator (SRA). These findings highlight a new level of regulation in nuclear receptor (NR)-mediated transcriptional responses. We have characterised the RNA association and activity of the human Pus1p enzyme with its unusual SRA substrate. We validate that the minimal RNA fragment within SRA, named H7, is necessary for both the association and modification by hPus1p. Furthermore, we have determined the crystal structure of the catalytic domain of hPus1p at 2.0 A resolution, alone and in a complex with several molecules present during crystallisation. This model shows an extended C-terminal helix specifically found in the eukaryotic protein, which may prevent the enzyme from forming a homodimer, both in the crystal lattice and in solution. Our biochemical and structural data help to understand the hPus1p active site architecture, and detail its particular requirements with regard to one of its nuclear substrates, the non-coding RNA SRA. Steroid receptor RNA activator (SRA) modification by the human pseudouridine synthase 1 (hPus1p): RNA binding, activity, and atomic model.,Huet T, Miannay FA, Patton JR, Thore S PLoS One. 2014 Apr 10;9(4):e94610. doi: 10.1371/journal.pone.0094610. eCollection, 2014. PMID:24722331[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
Contents | ||||||||||||||||||||||
