1xq3
From Proteopedia
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Crystal structure of the human androgen receptor ligand binding domain bound with R1881
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Overview
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.
Disease
Known diseases associated with this structure: Androgen insensitivity OMIM:[313700], Breast cancer, male, with Reifenstein syndrome OMIM:[313700], Hypospadias, perineal OMIM:[313700], Prostate cancer OMIM:[313700], Prostate cancer, susceptibility to OMIM:[313700], Spinal and bulbar muscular atrophy of Kennedy OMIM:[313700]
About this Structure
1XQ3 is a Single protein structure of sequence from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structural basis for androgen receptor interdomain and coactivator interactions suggests a transition in nuclear receptor activation function dominance., He B, Gampe RT Jr, Kole AJ, Hnat AT, Stanley TB, An G, Stewart EL, Kalman RI, Minges JT, Wilson EM, Mol Cell. 2004 Nov 5;16(3):425-38. PMID:15525515
Page seeded by OCA on Fri Feb 15 17:10:05 2008
