The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis.
The RIP1/RIP3 necrosome forms a functional amyloid signaling complex required for programmed necrosis.
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DOI：
10.1016/j.cell.2012.06.019
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发表时间：
2012-07-20
期刊：
影响因子：
64.5
通讯作者：
Wu H
中科院分区：
文献类型：
--
作者：
Li J;McQuade T;Siemer AB;Napetschnig J;Moriwaki K;Hsiao YS;Damko E;Moquin D;Walz T;McDermott A;Chan FK;Wu H
RIP1和RIP3是肿瘤坏死因子诱导的程序性坏死的中心角色。在这里，我们报道了RIP1和RIP3的RIP同型相互作用基序(RHIM)介导了异源二聚体丝状结构的组装。硫代黄素T(THT)和刚果红(CR)结合、圆二色谱、红外光谱、X-射线衍射和固体核磁共振表明，这些纤维具有典型的β-淀粉样蛋白特征。结构性淀粉样蛋白核心定位于RIP1和RIP3，两侧是移动区。从坏死细胞分离的内源性RIP1/RIP3复合体结合Tht，超稳定，具有纤维状核心结构，而坏死部分被Tht，CR和另一种淀粉样染料HBx抑制。RIP1和RIP3的RHIMs的突变在相互作用中存在缺陷，从而影响体内的簇形成、激酶激活和程序性坏死。目前的研究深入了解了当RIP激酶被触发以执行不同的信号结果时发生的结构变化，并将淀粉样蛋白的领域扩展到复杂的形成和信号传递。
RIP1 and RIP3 kinases are central players in TNF-induced programmed necrosis. Here, we report that the RIP homotypic interaction motifs (RHIMs) of RIP1 and RIP3 mediate the assembly of heterodimeric filamentous structures. The fibrils exhibit classical characteristics of β-amyloids, as shown by Thioflavin T (ThT) and Congo red (CR) binding, circular dichroism, infrared spectroscopy, X-ray diffraction, and solid-state NMR. Structured amyloid cores are mapped in RIP1 and RIP3 that are flanked by regions of mobility. The endogenous RIP1/RIP3 complex isolated from necrotic cells binds ThT, is ultrastable, and has a fibrillar core structure, whereas necrosis is partially inhibited by ThT, CR, and another amyloid dye, HBX. Mutations in the RHIMs of RIP1 and RIP3 that are defective in the interaction compromise cluster formation, kinase activation, and programmed necrosis in vivo. The current study provides insight into the structural changes that occur when RIP kinases are triggered to execute different signaling outcomes and expands the realm of amyloids to complex formation and signaling.
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影响因子：
64.8
作者：
Oberst, Andrew;Dillon, Christopher P.;Weinlich, Ricardo;McCormick, Laura L.;Fitzgerald, Patrick;Pop, Cristina;Hakem, Razq;Salvesen, Guy S.;Green, Douglas R.
通讯作者：
Green, Douglas R.
影响因子：
4.4
作者：
Kaiser, WJ;Offermann, MK
通讯作者：
Offermann, MK
影响因子：
10.5
作者：
Lin, Y;Devin, A;Liu, ZG
通讯作者：
Liu, ZG
RIP3 的裂解通过去除激酶结构域使其不依赖 caspase 的细胞凋亡途径失活
影响因子：
4.8
作者：
Feng, Shanshan;Yang, Yonghui;Wu, Mian
通讯作者：
Wu, Mian
DOI：
10.1093/jmicro/dfp036
发表时间：
2010-02-01
期刊：
JOURNAL OF ELECTRON MICROSCOPY
影响因子：
--
作者：
Li, Zongli;Hite, Richard K.;Walz, Thomas
通讯作者：
Walz, Thomas