4MCF

Crystal structure of the Gas5 GRE Mimic

4MCF の概要

• エントリーDOI: 10.2210/pdb4mcf/pdb
• 分子名称: Gas5 GREM Fwd, Gas5 GREM Rev, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: rna double helix, rna
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 27028.44

構造登録者

Hudson, W.H.,Ortlund, E.A. (登録日: 2013-08-21, 公開日: 2014-11-12, 最終更新日: 2024-02-28)

主引用文献

Hudson, W.H.,Pickard, M.R.,de Vera, I.M.,Kuiper, E.G.,Mourtada-Maarabouni, M.,Conn, G.L.,Kojetin, D.J.,Williams, G.T.,Ortlund, E.A.
Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate.
Nat Commun, 5:5395-5395, 2014

PubMed Abstract: The majority of the eukaryotic genome is transcribed, generating a significant number of long intergenic noncoding RNAs (lincRNAs). Although lincRNAs represent the most poorly understood product of transcription, recent work has shown lincRNAs fulfill important cellular functions. In addition to low sequence conservation, poor understanding of structural mechanisms driving lincRNA biology hinders systematic prediction of their function. Here we report the molecular requirements for the recognition of steroid receptors (SRs) by the lincRNA growth arrest-specific 5 (Gas5), which regulates steroid-mediated transcriptional regulation, growth arrest and apoptosis. We identify the functional Gas5-SR interface and generate point mutations that ablate the SR-Gas5 lincRNA interaction, altering Gas5-driven apoptosis in cancer cell lines. Further, we find that the Gas5 SR-recognition sequence is conserved among haplorhines, with its evolutionary origin as a splice acceptor site. This study demonstrates that lincRNAs can recognize protein targets in a conserved, sequence-specific manner in order to affect critical cell functions.

PubMed: 25377354
DOI: 10.1038/ncomms6395

実験手法

X-RAY DIFFRACTION (1.899 Å)