ATG9B is a tissue-specific homotrimeric lipid scramblase that can compensate for ATG9A (1).pdf (6.72 MB)
ATG9B is a tissue-specific homotrimeric lipid scramblase that can compensate for ATG9A.
journal contribution
posted on 2024-03-13, 10:12 authored by George N Chiduza, Acely Garza-Garcia, Eugenia Almacellas, Stefano De Tito, Valerie E Pye, Alexander R van Vliet, Peter Cherepanov, Sharon A ToozeMacroautophagy/autophagy is a fundamental aspect of eukaryotic biology, and the autophagy-related protein ATG9A is part of the core machinery facilitating this process. In addition to ATG9A vertebrates encode ATG9B, a poorly characterized paralog expressed in a subset of tissues. Herein, we characterize the structure of human ATG9B revealing the conserved homotrimeric quaternary structure and explore the conformational dynamics of the protein. Consistent with the experimental structure and computational chemistry, we establish that ATG9B is a functional lipid scramblase. We show that ATG9B can compensate for the absence of ATG9A in starvation-induced autophagy displaying similar subcellular trafficking and steady-state localization. Finally, we demonstrate that ATG9B can form a heteromeric complex with ATG2A. By establishing the molecular structure and function of ATG9B, our results inform the exploration of niche roles for autophagy machinery in more complex eukaryotes and reveal insights relevant across species.
Funding
Crick (Grant ID: CC2058, Grant title: Cherepanov CC2058) Crick (Grant ID: CC2134, Grant title: Tooze CC2134) Crick (Grant ID: CC2000, Grant title: Carvalho CC2000)
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- Signalling & Oncogenes
- Chemical Biology & High Throughput
- Ecology,Evolution & Ethology
- Infectious Disease
- Genetics & Genomics
- Metabolism
- Computational & Systems Biology
- Genome Integrity & Repair
- Model organisms
- Biochemistry & Proteomics
- Structural Biology & Biophysics
- Cell Biology
- Imaging
- Cell Cycle & Chromosomes
Keywords
ATG9AautophagyCryo-EMmembrane protein dynamicsphagophorescramblasesingle-particle analysiscryo-EMTooze CC2134Cherepanov CC2058Carvalho CC2000SB-ackNans, AndreaLang, DannyRoche, JohnGavrielides, MikisButt, MatthewSC-ackRI-ackCS-ackPC-ack0601 Biochemistry and Cell BiologyBiochemistry & Molecular Biology3101 Biochemistry and cell biology
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