Laboratory of Molecular Biology, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Autophagy. 2012 Dec;8(12):1851-2. doi: 10.4161/auto.22077. Epub 2012 Sep 20.
The key autophagic lipid sensors are Atg18 in yeast and the WIPI proteins in mammals. Atg18 and the WIPIs belong to the PROPPIN family of proteins. PROPPINs are seven- bladed β-propellers that bind to phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,5-bisphosphate [PtdIns(3,5)P2]. In order to understand how PROPPINs bind phosphoinositides, we have determined the crystal structure of a representative, biochemically tractable PROPPIN, Hsv2 of Kluveromyces lactis. The structure revealed that PROPPINs contain two phosphoinositide binding sites which cooperate with a hydrophobic anchoring loop in membrane binding. These three binding elements cooperate in function, as demonstrated by the incremental loss of function in Atg18 mutants impaired in combinations of the two phosphoinositide binding sites and the hydrophobic loop.
关键的自噬脂质传感器是酵母中的 Atg18 和哺乳动物中的 WIPI 蛋白。Atg18 和 WIPI 属于 PROPPIN 蛋白家族。PROPPIN 是一种七叶β-螺旋桨，与磷脂酰肌醇 3-磷酸（PtdIns3P）和磷脂酰肌醇 3,5-二磷酸[PtdIns(3,5)P2]结合。为了了解 PROPPINs 如何结合磷酸肌醇，我们已经确定了一种有代表性的、生化上可处理的 PROPPIN，即乳克鲁维酵母的 Hsv2 的晶体结构。该结构表明，PROPPINs 包含两个磷酸肌醇结合位点，与膜结合中的疏水性锚定环合作。这三个结合元件协同发挥功能，正如 Atg18 突变体在两个磷酸肌醇结合位点和疏水性环的组合中功能受损的情况下，功能呈递次丧失所证明的那样。
