4OED

Crystal structure of AR-LBD bound with co-regulator peptide

Summary for 4OED

• Entry DOI: 10.2210/pdb4oed/pdb
• Related: 4OEA 4OEY 4OEZ 4OFR 4OFU 4OGH 4OH5 4OH6 4OHA 4OIL 4OIU 4OJ9 4OJB 4OK1 4OKB 4OKT 4OKW 4OKX 4OLM
• Descriptor: Androgen receptor, Protein BUD31 homolog, SULFATE ION, ... (5 entities in total)
• Functional Keywords: alpha-helix, hormone/growth factor receptor, phosphorylation, hormone receptor-peptide complex, hormone receptor/peptide
• Biological source: Homo sapiens (human); More
• Cellular location: Nucleus: P10275 P41223
• Total number of polymer chains: 2
• Total formula weight: 31491.98

Authors

Liu, J.S.,Hsu, C.L.,Wu, W.G. (deposition date: 2014-01-13, release date: 2014-08-20, Last modification date: 2023-09-20)

Primary citation

Hsu, C.L.,Liu, J.S.,Wu, P.L.,Guan, H.H.,Chen, Y.L.,Lin, A.C.,Ting, H.J.,Pang, S.T.,Yeh, S.D.,Ma, W.L.,Chen, C.J.,Wu, W.G.,Chang, C.
Identification of a new androgen receptor (AR) co-regulator BUD31 and related peptides to suppress wild-type and mutated AR-mediated prostate cancer growth via peptide screening and X-ray structure analysis.
Mol Oncol, 8:1575-1587, 2014

PubMed Abstract: Treatment with individual anti-androgens is associated with the development of hot-spot mutations in the androgen receptor (AR). Here, we found that anti-androgens-mt-ARs have similar binary structure to the 5α-dihydrotestosterone-wt-AR. Phage display revealed that these ARs bound to similar peptides, including BUD31, containing an Fxx(F/H/L/W/Y)Y motif cluster with Tyr in the +5 position. Structural analyses of the AR-LBD-BUD31 complex revealed formation of an extra hydrogen bond between the Tyr+5 residue of the peptide and the AR. Functional studies showed that BUD31-related peptides suppressed AR transactivation, interrupted AR N-C interaction, and suppressed AR-mediated cell growth. Combination of peptide screening and X-ray structure analysis may serve as a new strategy for developing anti-ARs that simultaneously suppress both wt and mutated AR function.

PubMed: 25091737
DOI: 10.1016/j.molonc.2014.06.009

Experimental method

X-RAY DIFFRACTION (2.79 Å)