4NBO

Human steroid receptor RNA activator protein carboxy-terminal domain

4NBO の概要

• エントリーDOI: 10.2210/pdb4nbo/pdb
• 分子名称: Steroid receptor RNA activator 1 (1 entity in total)
• 機能のキーワード: 5-helix bundle, transcription
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q9HD15
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 25487.25

構造登録者

Mckay, D.B.,Xi, L.,Barthel, K.K.B.,Cech, T.C. (登録日: 2013-10-23, 公開日: 2014-02-05, 最終更新日: 2023-09-20)

主引用文献

McKay, D.B.,Xi, L.,Barthel, K.K.,Cech, T.R.
Structure and function of steroid receptor RNA activator protein, the proposed partner of SRA noncoding RNA.
J.Mol.Biol., 426:1766-1785, 2014

PubMed Abstract: In a widely accepted model, the steroid receptor RNA activator protein (SRA protein; SRAP) modulates the transcriptional regulatory activity of SRA RNA by binding a specific stem-loop of SRA. We first confirmed that SRAP is present in the nucleus as well as the cytoplasm of MCF-7 breast cancer cells, where it is expressed at the level of about 10(5) molecules per cell. However, our SRAP-RNA binding experiments, both in vitro with recombinant protein and in cultured cells with plasmid-expressed protein and RNA, did not reveal a specific interaction between SRAP and SRA. We determined the crystal structure of the carboxy-terminal domain of human SRAP and found that it does not have the postulated RRM (RNA recognition motif). The structure is a five-helix bundle that is distinct from known RNA-binding motifs and instead is similar to the carboxy-terminal domain of the yeast spliceosome protein PRP18, which stabilizes specific protein-protein interactions within a multisubunit mRNA splicing complex. SRA binding experiments with this domain gave negative results. Transcriptional regulation by SRA/SRAP was examined with siRNA knockdown. Effects on both specific estrogen-responsive genes and genes identified by RNA-seq as candidates for regulation were examined in MCF-7 cells. Only a small effect (~20% change) on one gene resulting from depletion of SRA/SRAP could be confirmed. We conclude that the current model for SRAP function must be reevaluated; we suggest that SRAP may function in a different context to stabilize specific intermolecular interactions in the nucleus.

PubMed: 24486609
DOI: 10.1016/j.jmb.2014.01.006

実験手法

X-RAY DIFFRACTION (2.807 Å)