National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)
HD8818
United States
Welch Foundation
Q-1967-20180324
United States
Citation
Journal: Mol Cell / Year: 2020 Title: Structural Insights of Transcriptionally Active, Full-Length Androgen Receptor Coactivator Complexes. Authors: Xinzhe Yu / Ping Yi / Ross A Hamilton / Hong Shen / Muyuan Chen / Charles E Foulds / Michael A Mancini / Steven J Ludtke / Zhao Wang / Bert W O'Malley / Abstract: Steroid receptors activate gene transcription by recruiting coactivators to initiate transcription of their target genes. For most nuclear receptors, the ligand-dependent activation function domain-2 ...Steroid receptors activate gene transcription by recruiting coactivators to initiate transcription of their target genes. For most nuclear receptors, the ligand-dependent activation function domain-2 (AF-2) is a primary contributor to the nuclear receptor (NR) transcriptional activity. In contrast to other steroid receptors, such as ERα, the activation function of androgen receptor (AR) is largely dependent on its ligand-independent AF-1 located in its N-terminal domain (NTD). It remains unclear why AR utilizes a different AF domain from other receptors despite that NRs share similar domain organizations. Here, we present cryoelectron microscopy (cryo-EM) structures of DNA-bound full-length AR and its complex structure with key coactivators, SRC-3 and p300. AR dimerization follows a unique head-to-head and tail-to-tail manner. Unlike ERα, AR directly contacts a single SRC-3 and p300. The AR NTD is the primary site for coactivator recruitment. The structures provide a basis for understanding assembly of the AR:coactivator complex and its domain contributions for coactivator assembly and transcriptional regulation.
History
Deposition
May 29, 2020
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Header (metadata) release
Jul 15, 2020
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Map release
Jul 15, 2020
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Update
Sep 16, 2020
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Current status
Sep 16, 2020
Processing site: RCSB / Status: Released
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Structure visualization
Movie
Surface view with section colored by density value
Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 291 K / Instrument: FEI VITROBOT MARK IV
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Electron microscopy
Microscope
JEOL 3200FSC
Specialist optics
Energy filter - Slit width: 20 eV
Image recording
Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Detector mode: SUPER-RESOLUTION / Number real images: 5741 / Average exposure time: 10.0 sec. / Average electron dose: 50.0 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron optics
Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD
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