Architecture of the Atg17 complex as a scaffold for autophagosome biogenesis.

Architecture of the Atg17 complex as a scaffold for autophagosome biogenesis.
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ATG17复合物的结构是自噬体生物发生的支架。

DOI:
10.1016/j.cell.2012.11.028
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发表时间:
2012-12-21
期刊:
影响因子:
64.5
通讯作者:
Hurley JH
Hurley JH
中科院分区:
生物学1区
文献类型:
--
作者:
Ragusa MJ;Stanley RE;Hurley JH

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Macroautophagy is a bulk clearance mechanism in which the double-membraned phagophore grows and engulfs cytosolic material. In yeast, the phagophore nucleates from a cluster of 20-30 nm diameter Atg9-containing vesicles located at a multiprotein assembly known as the preautophagosomal structure (PAS). The crystal structure of a 2:2:2 complex of the earliest-acting PAS proteins, Atg17, Atg29, and Atg31, was solved at 3.05 Å resolution. Atg17 is crescent-shaped with a 10 nm radius of curvature. Dimerization of the Atg17-Atg31-Atg29 complex is critical for both PAS formation and autophagy and each dimer contains two separate and complete crescents. Upon induction of autophagy, Atg17-Atg31-Atg29 assembles with Atg1 and Atg13, which in turn initiates the formation of the phagophore. The C-terminal EAT domain of Atg1 was shown to sense membrane curvature, dimerize, and tether lipid vesicles. These data suggest a structural mechanism for the organization of Atg9 vesicles into the early phagophore.
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