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Abstract：
A multifunctional role of Atg8-family proteins (Atg8 from yeast and human LC3 and GABARAP subfamilies, all referred to here as ATG8s) in macroautophagy/autophagy is carried out by two protein domains, the N-terminal helical domain (NHD) and ubiquitin-like (UBL) domain. Previous studies showed that the NHD of PE-conjugated ATG8s mediates membrane hemifusion via a direct interaction with lipids in trans-membrane association, which would require the NHD in lipidated ATG8s to adopt a solvent-oriented, \"open\", conformation that unmasks a UBL domain surface needed for membrane tethering. A purpose of the \"closed\" conformation of the NHD masking the tethering surface on the UBL domain, a conformation seen in the most structures of non-lipidated ATG8s, remained elusive. A recent study by Zhang et al. discussed in this article, showed that the N terminus of lipidated human ATG8s adopts the \"closed\" conformation when it interacts with the membrane in cis-membrane association, i.e. with the same membrane ATG8 is anchored to. This finding suggests functions for two distinct conformations of the NHD in lipidated ATG8s and raises questions about determinants controlling cis- or trans-membrane associations of the NHD in ATG8-PE.Abbreviations: AIM, Atg8-family interacting motif; 3D-CLEM, three-dimensional correlative light and electron microscopy; FRET, Förster/fluorescence resonance energy transfer; LIR, LC3-interacting motif; MD, molecular dynamics; NHD, N-terminal helical domain; UBL, ubiquitin-like.
摘要：
Atg8家族蛋白的多功能作用（来自酵母和人类LC3和GABARAP亚家族的Atg8，这里全部称为ATG8）中的巨自噬/自噬由两个蛋白质结构域进行，N端螺旋结构域(NHD)和泛素样(UBL)结构域。以前的研究表明，PE结合ATG8s的NHD通过与跨膜缔合中的脂质直接相互作用介导膜半融合，这将要求脂化ATG8中的NHD采用溶剂导向，\"打开\",解开膜束缚所需的UBL结构域表面的构象。NHD的“封闭”构象掩盖UBL域上的束缚表面的目的，在非脂化ATG8的大多数结构中看到的构象，仍然难以捉摸。Zhang等人最近的一项研究。在这篇文章中讨论，表明脂化的人ATG8的N末端在顺膜缔合中与膜相互作用时采用“封闭”构象，即与ATG8锚定到相同的膜。这一发现表明，在脂化的ATG8中，NHD的两种不同构象具有功能，并提出了有关控制ATG8-PE中NHD顺膜或跨膜缔合的决定簇的问题。
