The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization
The L3 loop and C-terminal phosphorylation jointly define Smad protein trimerization
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DOI：
10.1038/84995
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发表时间：
2001-03-01
期刊：
影响因子：
--
通讯作者：
Lin, K
中科院分区：
文献类型：
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作者：
Chacko, BM;Qin, B;Lin, K
Smad蛋白介导转化生长因子β反应。R-Smads的C-末端磷酸化导致Smad 4的募集和活性信号复合物的形成。我们研究了磷酸化诱导的Smad复合物形成的机制与活化的假磷酸化Smad 3。假磷酸化的Smad 3具有更大的同源三聚化倾向，并招募Smad 4形成含有两个Smad 3和一个Smad 4的异源三聚体。三聚体相互作用是通过致瘤突变映射的保守界面介导的。此外，L3环内的保守Arg残基，位于邻近亚基的C-末端磷酸化位点附近，对于三聚化是必需的。我们提出，磷酸化的C-末端残基与相邻亚基的L3环相互作用，以稳定三聚体相互作用。
Smad proteins mediate the transforming growth factor beta responses. C-terminal phosphorylation of R-Smads leads to the recruitment of Smad4 and the formation of active signaling complexes. We investigated the mechanism of phosphorylation-induced Smad complex formation with an activating pseudo-phosphorylates Smad3. Pseudo-phosphorylated Smad3 has a greater propensity to homotrimerize, and recruits Smad4 to form a heterotrimer containing two Smad3 and one Smad4. The trimeric interaction is mediated through conserved interfaces to which tumorigenic mutations map. Furthermore, a conserved Arg residue within the L3 loop, located near the C-terminal phosphorylation sites of the neighboring subunit, is essential for trimerization. We propose that the phosphorylated C-terminal residues interact with the L3 loop of the neighboring subunit to stabilize the trimer interaction.