生物
细胞生物学
自噬
磷脂酶
脂质双层
自噬体
膜
膜蛋白
生物物理学
生物化学
磷脂
磷脂酰丝氨酸
细胞凋亡
作者
Alexander R. van Vliet,George N. Chiduza,Sarah Maslen,V.E. Pye,Dhira Joshi,Stefano De Tito,Harold B.J. Jefferies,Evangelos Christodoulou,Chloë Roustan,Emma K. Punch,Javier H. Hervás,Nicola O’Reilly,J. Mark Skehel,Peter Cherepanov,Sharon A. Tooze
出处
期刊:Molecular Cell
[Elsevier]
日期:2022-11-01
卷期号:82 (22): 4324-4339.e8
被引量:50
标识
DOI:10.1016/j.molcel.2022.10.017
摘要
ATG9A and ATG2A are essential core members of the autophagy machinery. ATG9A is a lipid scramblase that allows equilibration of lipids across a membrane bilayer, whereas ATG2A facilitates lipid flow between tethered membranes. Although both have been functionally linked during the formation of autophagosomes, the molecular details and consequences of their interaction remain unclear. By combining data from peptide arrays, crosslinking, and hydrogen-deuterium exchange mass spectrometry together with cryoelectron microscopy, we propose a molecular model of the ATG9A-2A complex. Using this integrative structure modeling approach, we identify several interfaces mediating ATG9A-2A interaction that would allow a direct transfer of lipids from ATG2A into the lipid-binding perpendicular branch of ATG9A. Mutational analyses combined with functional activity assays demonstrate their importance for autophagy, thereby shedding light on this protein complex at the heart of autophagy.
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