1XOW

Crystal structure of the human androgen receptor ligand binding domain bound with an androgen receptor NH2-terminal peptide, AR20-30, and R1881

Summary for 1XOW

• Entry DOI: 10.2210/pdb1xow/pdb
• Related: 1E3G 1I37 1XOW 1XQ2 1XQ3
• Descriptor: androgen receptor, decamer fragment of androgen receptor, (17BETA)-17-HYDROXY-17-METHYLESTRA-4,9,11-TRIEN-3-ONE, ... (4 entities in total)
• Functional Keywords: crystal structure; human androgen receptor ligand binding domain; androgen receptor nh2-terminal peptide ar20-30; r1881, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus : P10275 P10275
• Total number of polymer chains: 2
• Total formula weight: 30597.88

Authors

He, B.,Gampe Jr., R.T.,Kole, A.J.,Hnat, A.T.,Stanley, T.B.,An, G.,Stewart, E.L.,Kalman, R.I.,Minges, J.T.,Wilson, E.M. (deposition date: 2004-10-07, release date: 2004-11-16, Last modification date: 2023-08-23)

Primary citation

He, B.,Gampe Jr., R.T.,Kole, A.J.,Hnat, A.T.,Stanley, T.B.,An, G.,Stewart, E.L.,Kalman, R.I.,Minges, J.T.,Wilson, E.M.
Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance
Mol.Cell, 16:425-438, 2004

PubMed Abstract: The androgen receptor (AR) is required for male sex development and contributes to prostate cancer cell survival. In contrast to other nuclear receptors that bind the LXXLL motifs of coactivators, the AR ligand binding domain is preferentially engaged in an interdomain interaction with the AR FXXLF motif. Reported here are crystal structures of the ligand-activated AR ligand binding domain with and without bound FXXLF and LXXLL peptides. Key residues that establish motif binding specificity are identified through comparative structure-function and mutagenesis studies. A mechanism in prostate cancer is suggested by a functional AR mutation at a specificity-determining residue that recovers coactivator LXXLL motif binding. An activation function transition hypothesis is proposed in which an evolutionary decline in LXXLL motif binding parallels expansion and functional dominance of the NH(2)-terminal transactivation domain in the steroid receptor subfamily.

PubMed: 15525515
DOI: 10.1016/j.molcel.2004.09.036

Experimental method

X-RAY DIFFRACTION (1.8 Å)