7ZTX
Crystal structure of mutant AR-LBD (F755V) bound to dihydrotestosterone
Summary for 7ZTX
| Entry DOI | 10.2210/pdb7ztx/pdb |
| Related | 7ZTV |
| Descriptor | Androgen receptor, 5-ALPHA-DIHYDROTESTOSTERONE, SULFATE ION, ... (5 entities in total) |
| Functional Keywords | hormone receptor, nuclear receptor, dht receptor, dna binding protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 29549.68 |
| Authors | Alegre-Marti, A.,Jimenez-Panizo, A.,Estebanez-Perpina, E.,Fuentes-Prior, P. (deposition date: 2022-05-11, release date: 2023-03-22, Last modification date: 2024-02-07) |
| Primary citation | Alegre-Marti, A.,Jimenez-Panizo, A.,Martinez-Tebar, A.,Poulard, C.,Peralta-Moreno, M.N.,Abella, M.,Anton, R.,Chinas, M.,Eckhard, U.,Piulats, J.M.,Rojas, A.M.,Fernandez-Recio, J.,Rubio-Martinez, J.,Le Romancer, M.,Aytes, A.,Fuentes-Prior, P.,Estebanez-Perpina, E. A hotspot for posttranslational modifications on the androgen receptor dimer interface drives pathology and anti-androgen resistance. Sci Adv, 9:eade2175-eade2175, 2023 Cited by PubMed Abstract: Mutations of the androgen receptor (AR) associated with prostate cancer and androgen insensitivity syndrome may profoundly influence its structure, protein interaction network, and binding to chromatin, resulting in altered transcription signatures and drug responses. Current structural information fails to explain the effect of pathological mutations on AR structure-function relationship. Here, we have thoroughly studied the effects of selected mutations that span the complete dimer interface of AR ligand-binding domain (AR-LBD) using x-ray crystallography in combination with in vitro, in silico, and cell-based assays. We show that these variants alter AR-dependent transcription and responses to anti-androgens by inducing a previously undescribed allosteric switch in the AR-LBD that increases exposure of a major methylation target, Arg. We also corroborate the relevance of residues Arg and Tyr for AR dimerization and function. Together, our results reveal allosteric coupling of AR dimerization and posttranslational modifications as a disease mechanism with implications for precision medicine. PubMed: 36921044DOI: 10.1126/sciadv.ade2175 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.89 Å) |
Structure validation
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