4NZ6

Steroid receptor RNA Activator (SRA) modification by the human Pseudouridine Synthase 1 (hPus1p): RNA binding, activity, and atomic model

Summary for 4NZ6

• Entry DOI: 10.2210/pdb4nz6/pdb
• Related: 4NZ7
• Descriptor: tRNA pseudouridine synthase A, mitochondrial, 1,2-ETHANEDIOL, TRIETHYLENE GLYCOL, ... (6 entities in total)
• Functional Keywords: nuclear receptor coactivator, steroid receptor rna activator, pseudouridylation, nucleus, mitochondrial, isomerase
• Biological source: Homo sapiens (human)
• Cellular location: Isoform 1: Mitochondrion. Isoform 2: Nucleus: Q9Y606
• Total number of polymer chains: 2
• Total formula weight: 71847.31

Authors

Huet, T.,Thore, S. (deposition date: 2013-12-11, release date: 2014-05-21, Last modification date: 2024-03-20)

Primary citation

Huet, T.,Miannay, F.-A.,Patton, J.R.,Thore, S.
Steroid Receptor RNA Activator (SRA) Modification by the Human Pseudouridine Synthase 1 (hPus1p): RNA Binding, Activity, and Atomic Model
Plos One, 9:e94610-e94610, 2014

PubMed Abstract: The 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 Å 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.

PubMed: 24722331
DOI: 10.1371/journal.pone.0094610

Experimental method

X-RAY DIFFRACTION (2 Å)