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TitleAtg18 oligomer organization in assembled tubes and on lipid membrane scaffolds.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 8086, Year 2023
Publish dateDec 6, 2023
AuthorsDaniel Mann / Simon A Fromm / Antonio Martinez-Sanchez / Navin Gopaldass / Ramona Choy / Andreas Mayer / Carsten Sachse /
PubMed AbstractAutophagy-related protein 18 (Atg18) participates in the elongation of early autophagosomal structures in concert with Atg2 and Atg9 complexes. How Atg18 contributes to the structural coordination of ...Autophagy-related protein 18 (Atg18) participates in the elongation of early autophagosomal structures in concert with Atg2 and Atg9 complexes. How Atg18 contributes to the structural coordination of Atg2 and Atg9 at the isolation membrane remains to be understood. Here, we determined the cryo-EM structures of Atg18 organized in helical tubes, Atg18 oligomers in solution as well as on lipid membrane scaffolds. The helical assembly is composed of Atg18 tetramers forming a lozenge cylindrical lattice with remarkable structural similarity to the COPII outer coat. When reconstituted with lipid membranes, using subtomogram averaging we determined tilted Atg18 dimer structures bridging two juxtaposed lipid membranes spaced apart by 80 Å. Moreover, lipid reconstitution experiments further delineate the contributions of Atg18's FRRG motif and the amphipathic helical extension in membrane interaction. The observed structural plasticity of Atg18's oligomeric organization and membrane binding properties provide a molecular framework for the positioning of downstream components of the autophagy machinery.
External linksNat Commun / PubMed:38057304 / PubMed Central
MethodsEM (helical sym.) / EM (single particle) / EM (subtomogram averaging)
Resolution3.3 - 26.0 Å
Structure data

15408

8afq

EMDB-15408, PDB-8afq:
Tube assembly of Atg18-PR72AA
Method: EM (helical sym.) / Resolution: 3.3 Å

15410

8afw

EMDB-15410, PDB-8afw:
Tube assembly of Atg18-WT
Method: EM (helical sym.) / Resolution: 3.8 Å

15411

8afx

EMDB-15411, PDB-8afx:
Single particle structure of Atg18-WT
Method: EM (single particle) / Resolution: 4.8 Å

15412

8afy

EMDB-15412, PDB-8afy:
Subtomogram average of membrane-bound Atg18 oligomers
Method: EM (subtomogram averaging) / Resolution: 26.0 Å

Source
  • saccharomyces cerevisiae (brewer's yeast)
KeywordsMEMBRANE PROTEIN / autophagy / membrane remodeling / PIP binding / PI3P / PI(3 / 5)P2 / lipid binding protein

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