Conserved and unique features of the fission yeast core Atg1 complex

Although the human ULK complex mediates phagophore initiation similar to the budding yeast <i>Saccharomyces cerevisiae</i> Atg1 complex, this complex contains ATG101 but not Atg29 and Atg31. Here, we analyzed the fission yeast <i>Schizosaccharomyces pombe</i> Atg1 complex, which has a subunit composition that resembles the human ULK complex. Our pairwise coprecipitation experiments showed that while the interactions between Atg1, Atg13, and Atg17 are conserved, Atg101 does not bind Atg17. Instead, Atg101 interacts with the HORMA domain of Atg13 and this enhances the stability of both proteins. We also found that <i>S. pombe</i> Atg17, the putative scaffold subunit, adopts a rod-shaped structure with no discernible curvature. Interestingly, <i>S. pombe</i> Atg17 binds <i>S. cerevisiae</i> Atg13, Atg29, and Atg31 in vitro, but it cannot complement the function of <i>S. cerevisiae</i> Atg17 in vivo. Furthermore, <i>S. pombe</i> Atg101 cannot substitute for the function of <i>S. cerevisiae</i> Atg29 and Atg31 in vivo. Collectively, our work generates new insights into the subunit organization and structural properties of an Atg101-containing Atg1/ULK complex.

尽管人类ULK复合物（ULK complex）与出芽酵母酿酒酵母（*Saccharomyces cerevisiae*）的Atg1复合物功能类似，均可介导自噬前体起始过程，但人类ULK复合物含有ATG101亚基，却不包含Atg29与Atg31亚基。
本研究针对裂殖酵母粟酒裂殖酵母（*Schizosaccharomyces pombe*）的Atg1复合物展开分析，该复合物的亚基组成与人类ULK复合物高度相似。
我们的成对共沉淀实验结果表明：尽管Atg1、Atg13与Atg17之间的相互作用在进化中具有保守性，但Atg101并不会与Atg17结合。
与之相反，Atg101可与Atg13的HORMA结构域（HORMA domain）相互作用，该相互作用能够同时增强两种蛋白的稳定性。
我们还发现，粟酒裂殖酵母的Atg17——假定的支架亚基——呈无明显曲率的杆状结构。
有趣的是，粟酒裂殖酵母Atg17可在体外结合酿酒酵母的Atg13、Atg29与Atg31，但无法在体内互补酿酒酵母Atg17的功能。
此外，粟酒裂殖酵母Atg101也无法在体内替代酿酒酵母Atg29与Atg31的功能。
综上，本研究为包含ATG101的Atg1/ULK复合物的亚基组织形式与结构特性提供了新的见解。