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Atg7–Atg12 conjugation and autophagy are negatively regulated by the disordered region of Atg12

ABSTRACT: : The macroautophagy/autophagy machinery has two ubiquitin-like (UBL) conjugation systems. The Atg8/MAP1LC3/GABARAP (yeast/human) and Atg12/ATG12 proteins are UBL substrates for Atg7/ATG7, a non-canonical E1 enzyme, that thioesterifies its substrates; however, autophagy requires a much greater amount of conjugated Atg8 (Atg8–PE) than Atg12 (Atg12–Atg5). Exactly how Atg7/ATG7 distinguishes between its two substrates to facilitate this differential biogenesis remains elusive. Here, analyses of recombinant complexes of yeast proteins reveal that the N termini of Atg8 and Atg12 are structural determinants for conjugation to Atg7, but play no role in conjugation to Atg3 or Atg10, non-canonical E2 enzymes. The disordered N terminus of Atg12 is a protector of the Atg12 C terminus and a negative regulator of Atg7–Atg12 conjugation and autophagy, whereas the N-terminal helical domain in Atg8 promotes autophagy and has a high avidity to Atg7. We show that balanced autophagy requires different specific N termini attached to the UBL domains.

INSTRUMENT(S):

ORGANISM(S): Saccharomyces Cerevisiae (baker's Yeast)

SUBMITTER: Hana Popelka

LAB HEAD: Hana Popelka

PROVIDER: PXD077491 | Pride | 2026-05-05

REPOSITORIES: Pride

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			Action	DRS
	PRF_A_2023_D_KLIO_1153_65207.raw	Raw
	PRF_A_2023_D_KLIO_1153_65207_FixedPSM.msf	Msf
	PRF_Q_2024_D_KLIO_1166_65810.msf	Msf
	PRF_Q_2024_D_KLIO_1166_65810.raw	Raw
	PRF_Q_2024_D_KLIO_1328_70414.msf	Msf

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