Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci.
Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci.
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Suppressor of Fused 和 Gli/Ci 之间相互识别和调节的结构洞察
DOI:
10.1038/ncomms3608
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发表时间:
2013
影响因子:
16.6
通讯作者:
Wu G
中科院分区:
文献类型:
--
作者:
Zhang Y;Fu L;Qi X;Zhang Z;Xia Y;Jia J;Jiang J;Zhao Y;Wu G
Hedgehog (Hh) signaling regulates embryonic development and adult tissue homeostasis. Mutations of its pathway components including Suppressor of Fused (Sufu) and Gli/Ci predispose to cancers and congenital anomalies. The Sufu-Gli protein complex occupies a central position in the vertebrate Hh signaling pathway, especially in mammals. Here, structures of full-length human and Drosophila Sufu, the human Sufu-Gli1 complex, along with normal mode analysis and FRET measurement results, reveal that Sufu alternates between “open” and “closed” conformations. The “closed” form of Sufu is stabilized by Gli-binding and inhibited by Hh treatment, whereas the “open” state of Sufu is promoted by Gli-dissociation and Hh signaling. Mutations of critical interface residues disrupt the Sufu-Gli complex, and prevent Sufu from repressing Gli-mediated transcription, tethering Gli in the cytoplasm, and protecting Gli from the 26S proteasome-mediated degradation. Our study thus provides mechanistic insight into the mutual recognition and regulation between Sufu and Gli/Ci.
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影响因子:
64.8
作者:
KINZLER, KW;RUPPERT, JM;VOGELSTEIN, B
通讯作者:
VOGELSTEIN, B
DOI:
10.1107/s0907444904019158
发表时间:
2004-12-01
影响因子:
2.2
作者:
Emsley, P;Cowtan, K
通讯作者:
Cowtan, K
影响因子:
4.6
作者:
Kent, D;Bush, EW;Hooper, JE
通讯作者:
Hooper, JE
影响因子:
11.8
作者:
Jiang J;Hui CC
通讯作者:
Hui CC
影响因子:
14.9
作者:
Landau M;Mayrose I;Rosenberg Y;Glaser F;Martz E;Pupko T;Ben-Tal N
通讯作者:
Ben-Tal N