The selective autophagy pathways of xenophagy and mitophagy are initiated when the adaptor NDP52 recruits the ULK1 complex to autophagic cargo. Hydrogen-deuterium exchange coupled to mass spectrometry (HDX-MS) was used to map the membrane and NDP52 binding sites of the ULK1 complex to unique regions of the coiled coil of the FIP200 subunit. Electron microscopy of the full-length ULK1 complex shows that the FIP200 coiled coil projects away from the crescent-shaped FIP200 N-terminal domain dimer. NDP52 allosterically stimulates membrane-binding by FIP200 and the ULK1 complex by promoting a more dynamic conformation of the membrane-binding portion of the FIP200 coiled coil. Giant unilamellar vesicle (GUV) reconstitution confirmed that membrane recruitment by the ULK1 complex is triggered by NDP52 engagement. These data reveal how the allosteric linkage between NDP52 and the ULK1 complex could drive the first membrane recruitment event of phagophore biogenesis in xenophagy and mitophagy.

中文翻译：

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自噬适配器NDP52和FIP200卷曲螺旋变构激活ULK1复合膜募集

当衔接子NDP52将ULK1复合体募集到自噬货物时，就会启动异种和线粒体的选择性自噬途径。氢-氘交换质谱联用技术（HDX-MS）将ULK1复合物的膜和NDP52结合位点映射到FIP200亚基的卷曲螺旋的独特区域。全长ULK1复合物的电子显微镜显示，FIP200盘绕的线圈远离月牙形的FIP200 N端域二聚体。NDP52通过促进FIP200卷曲螺旋的膜结合部分更具动态构象，从而变构刺激FIP200和ULK1复合物的膜结合。巨大的单层囊泡（GUV）重组证实，ULK1复合物的膜募集是由NDP52参与触发的。