Signal Transduction by a Fungal NOD-Like Receptor Based on Propagation of a Prion Amyloid Fold
Signal Transduction by a Fungal NOD-Like Receptor Based on Propagation of a Prion Amyloid Fold
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DOI：
10.1371/journal.pbio.1002059
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发表时间：
2015-02-01
期刊：
影响因子：
9.8
通讯作者：
Saupe, Sven J.
中科院分区：
文献类型：
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作者：
Daskalov, Asen;Habenstein, Birgit;Saupe, Sven J.
在真菌Podospora anserina中，[Het-s]朊病毒通过激活HET-S孔形成蛋白诱导程序性细胞死亡。HET-s β-螺线管朊病毒折叠作为将HET-S朊病毒形成结构域转化为相同折叠的模板。这种转化反过来激活HET-S成孔结构域。紧邻het-S的基因编码NWD2，NWD2是一种Nod样受体（NLR），其N末端基序类似于β-螺线管折叠的基本重复单元。NLR是动物、植物和真菌中控制细胞死亡和宿主防御过程的免疫受体。我们已经提出，类似于[Het-s]，NWD2可以通过将其朊病毒形成区域转化为β螺线管折叠来激活HET-S孔形成蛋白。在这里，我们分析了NWD2诱导β螺线管朊病毒折叠形成的能力。我们表明，人工NWD2变体诱导形成的[Het-s]朊病毒，特别是在存在其同源配体。N-末端基序负责这种朊病毒诱导，预测影响β-螺线管折叠的突变会消除模板活性。在体外，N-末端基序组装成感染性朊病毒淀粉样蛋白，其显示类似于β-螺线管折叠的结构。在体内，NWD2 N-末端区域的组装形式激活HET-S孔形成蛋白。这项研究记录了β-螺线管折叠在真菌NLR功能中的作用，进一步强调了淀粉样蛋白和朊病毒样信号在免疫相关细胞命运途径中的普遍重要性。
In the fungus Podospora anserina, the [Het-s] prion induces programmed cell death by activating the HET-S pore-forming protein. The HET-s beta-solenoid prion fold serves as a template for converting the HET-S prion-forming domain into the same fold. This conversion, in turn, activates the HET-S pore-forming domain. The gene immediately adjacent to het-S encodes NWD2, a Nod-like receptor (NLR) with an N-terminal motif similar to the elementary repeat unit of the beta-solenoid fold. NLRs are immune receptors controlling cell death and host defense processes in animals, plants and fungi. We have proposed that, analogously to [Het-s], NWD2 can activate the HET-S pore-forming protein by converting its prion-forming region into the beta-solenoid fold. Here, we analyze the ability of NWD2 to induce formation of the beta-solenoid prion fold. We show that artificial NWD2 variants induce formation of the [Het-s] prion, specifically in presence of their cognate ligands. The N-terminal motif is responsible for this prion induction, and mutations predicted to affect the beta-solenoid fold abolish templating activity. In vitro, the N-terminal motif assembles into infectious prion amyloids that display a structure resembling the beta-solenoid fold. In vivo, the assembled form of the NWD2 N-terminal region activates the HET-S pore-forming protein. This study documenting the role of the beta-solenoid fold in fungal NLR function further highlights the general importance of amyloid and prion-like signaling in immunity-related cell fate pathways.