4MCE

Crystal structure of the Gas5 GRE Mimic

Summary for 4MCE

• Entry DOI: 10.2210/pdb4mce/pdb
• Descriptor: Gas5 GREM Fwd, Gas5 GREM Rev, SULFATE ION, ... (4 entities in total)
• Functional Keywords: rna double helix, rna
• Biological source: Homo sapiens; More
• Total number of polymer chains: 4
• Total formula weight: 13610.28

Authors

Hudson, W.H.,Ortlund, E.A. (deposition date: 2013-08-21, release date: 2014-09-24, Last modification date: 2024-02-28)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.205 Å)