A dynamic structural model for estrogen receptor-α activation by ligands, emphasizing the role of interactions between distant A and E domains

被引:111
作者
Métivier, R
Stark, A
Flouriot, G
Hübner, MR
Brand, H
Penot, G
Manu, D
Denger, S
Reid, G
Kos, M
Russell, RB
Kah, O
Pakdel, F [1 ]
Gannon, F
机构
[1] Univ Rennes 1, UMR CNRS 6026, Equipe EMR, F-35042 Rennes, France
[2] EMBL, D-69117 Heidelberg, Germany
关键词
D O I
10.1016/S1097-2765(02)00746-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The functional interplay between different domains of estrogen receptor-alpha (ERalpha, NR3A1) is responsible for the overall properties of the full-length protein. We previously identified an interaction between the N-terminal A and C-temninal domains, which we demonstrate here to repress ligand-independent transactivation and transirepression abilities of ERalpha. Using targeted mutations based on ERa structural models, we determine the basis for this interaction that defines a regulatory interplay between ERalpha A domain, corepressors, and ERalpha Helix 12 for binding to the same C-terminal surface. We propose a dynamic model where binding of different ligands influences the A/D-F domain interaction and results in specific functional outcomes. This model gives insights into the dynamic properties of full-length ERalpha and into the structure of unliganded ERalpha.
引用
收藏
页码:1019 / 1032
页数:14
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