Expression, purification and primary crystallographic study of human androgen receptor in complex with DNA and coactivator motifs.
The androgen receptor (AR) is a DNA-binding and hormone-activated transcription factor that plays critical roles in the development and progression of prostate cancer. The transcriptional function of AR is modulated by intermolecular interactions with DNA elements and coactivator proteins, as well as intramolecular interactions between AR domains; thus, the structural information from the full-length AR or a multi-domain fragment is essential for understanding the molecular basis of AR functions. Here we report the expression and purification of full-length AR protein and of a fragment containing its DNA-binding and ligand-binding domains connected by the hinge region in the presence of its natural ligand, dihydrotestosterone. Crystals of ligand-bound full-length AR and of the AR fragment in complex with DNA elements and coactivator motifs have been obtained and diffracted to low resolutions. These results help establish a foundation for pursuing further crystallographic studies of an AR/DNA complex.
Zhou
X Edward
XE
Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, NE Grand Rapids, MI 49503, USA. Edward.Zhou@vai.org
Suino-Powell
Kelly
K
Ludidi
Phumzile L
PL
McDonnell
Donald P
DP
Xu
H Eric
HE
D000595:Amino Acid Sequence; D001681:Biological Assay; D003460:Crystallization; D018360:Crystallography, X-Ray / Q000379:methods*; D004247:DNA / Q000378:metabolism*; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011944:Receptors, Androgen / Q000737:chemistry* / Q000302:isolation & purification* / Q000378:metabolism; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*
C410798:AR protein, human; D010455:Peptides; D011944:Receptors, Androgen; D015534:Trans-Activators; D004247:DNA