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The Structure of the Necrosome RIPK1-RIPK3 Core, a Human Hetero-Amyloid Signaling Complex.
Cell ( IF 45.5 ) Pub Date : 2018-04-19 , DOI: 10.1016/j.cell.2018.03.032 Miguel Mompeán 1 , Wenbo Li 2 , Jixi Li 3 , Ségolène Laage 2 , Ansgar B Siemer 2 , Gunes Bozkurt 4 , Hao Wu 4 , Ann E McDermott 2
Cell ( IF 45.5 ) Pub Date : 2018-04-19 , DOI: 10.1016/j.cell.2018.03.032 Miguel Mompeán 1 , Wenbo Li 2 , Jixi Li 3 , Ségolène Laage 2 , Ansgar B Siemer 2 , Gunes Bozkurt 4 , Hao Wu 4 , Ann E McDermott 2
Affiliation
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The RIPK1-RIPK3 necrosome is an amyloid signaling complex that initiates TNF-induced necroptosis, serving in human immune defense, cancer, and neurodegenerative diseases. RIPK1 and RIPK3 associate through their RIP homotypic interaction motifs with consensus sequences IQIG (RIPK1) and VQVG (RIPK3). Using solid-state nuclear magnetic resonance, we determined the high-resolution structure of the RIPK1-RIPK3 core. RIPK1 and RIPK3 alternately stack (RIPK1, RIPK3, RIPK1, RIPK3, etc.) to form heterotypic β sheets. Two such β sheets bind together along a compact hydrophobic interface featuring an unusual ladder of alternating Ser (from RIPK1) and Cys (from RIPK3). The crystal structure of a four-residue RIPK3 consensus sequence is consistent with the architecture determined by NMR. The RIPK1-RIPK3 core is the first detailed structure of a hetero-amyloid and provides a potential explanation for the specificity of hetero- over homo-amyloid formation and a structural basis for understanding the mechanisms of signal transduction.
中文翻译：
坏死体 RIPK1-RIPK3 核心的结构，一种人类异质淀粉样信号复合体。
RIPK1-RIPK3 necrosome 是一种淀粉样蛋白信号复合物，可启动 TNF 诱导的坏死性凋亡，用于人类免疫防御、癌症和神经退行性疾病。RIPK1 和 RIPK3 通过它们的 RIP 同型相互作用基序与共有序列 IQIG (RIPK1) 和 VQVG (RIPK3) 关联。使用固态核磁共振，我们确定了 RIPK1-RIPK3 核心的高分辨率结构。RIPK1 和 RIPK3 交替堆叠（RIPK1、RIPK3、RIPK1、RIPK3 等）形成异型 β 折叠。两个这样的 β 片层沿着一个紧凑的疏水界面结合在一起，该界面具有一个不同寻常的交替 Ser（来自 RIPK1）和 Cys（来自 RIPK3）的阶梯。四残基 RIPK3 共有序列的晶体结构与 NMR 确定的结构一致。
更新日期：2018-04-26
中文翻译：
坏死体 RIPK1-RIPK3 核心的结构，一种人类异质淀粉样信号复合体。
RIPK1-RIPK3 necrosome 是一种淀粉样蛋白信号复合物，可启动 TNF 诱导的坏死性凋亡，用于人类免疫防御、癌症和神经退行性疾病。RIPK1 和 RIPK3 通过它们的 RIP 同型相互作用基序与共有序列 IQIG (RIPK1) 和 VQVG (RIPK3) 关联。使用固态核磁共振，我们确定了 RIPK1-RIPK3 核心的高分辨率结构。RIPK1 和 RIPK3 交替堆叠（RIPK1、RIPK3、RIPK1、RIPK3 等）形成异型 β 折叠。两个这样的 β 片层沿着一个紧凑的疏水界面结合在一起，该界面具有一个不同寻常的交替 Ser（来自 RIPK1）和 Cys（来自 RIPK3）的阶梯。四残基 RIPK3 共有序列的晶体结构与 NMR 确定的结构一致。
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