选择性自噬受体识别底物的结构机制

自噬是将细胞质物质运送至溶酶体/液泡的过程，该过程对维持细胞稳态至关重要。自噬通常被认为是非特异性的，但一些货物蛋白可以通过特异的自噬受体运输。最近在裂殖酵母中发现一种特殊的由Nbr1介导的选择性自噬NVT通路，该通路通过内体，而不是双膜结构的自噬体，把细胞质中的水解酶Ape2 和Lap2运输到液泡。我们计划通过冷冻电镜技术来解析Nbr1和货物蛋白的高分辨率结构。我们的研究将为揭示Nbr1识别货物的特异性和多样性提供结构基础。

Autophagy delivers cytoplasmic materials to the lysosome/vacuole and is critical for maintaining cellular homeostasis. Autophagy is generally considered as a non-specific cellular process, yet some cargos have been found to be selectively transported by autophagy receptors. The autophagy receptor Nbr1 was recently found to mediate a novel selective autophagy pathway in the fission yeast. The Nbr1-mediated vacuolar targeting (NVT) pathway depends on endosome, but not the double-membraned autophagosome, for transporting cytosolic hydrolases Ape2 and Lap2 into vacuoles. We aim to determine high-resolution structures of Nbr1-cargo complexes by cryo-electron microscopy. Our study will illustrate the structural basis of specificity and diversity in Nbr1-mediated cargo recognition.