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Published on: June 7, 2024
Revisiting the evolution of the yeast Atg1 complex
Kha M Nguyen1, Hannah R Shariati1, Calvin K Yip1
1Life Sciences Institute, Department of Biochemistry and Molecular Biology, The University of British Columbia, Vancouver, Canada.
Abstract:
The budding yeast Saccharomyces cerevisiae Atg1 complex coordinates the initiation of nonselective autophagy and consists of the Atg1 kinase, Atg13 regulatory subunit, and an S-shaped scaffold formed by Atg17, Atg29, and Atg31. In contrast, the fission yeast Schizosaccharomyces pombe Atg1 complex incorporates Atg101 instead of Atg29 and Atg31 and features a rod-shaped Atg17 scaffold. The timing of this divergence and its impact on the structural evolution of Atg17 remain unclear. Our systematic composition analysis revealed that Atg101 is found in the Atg1 complex of several budding yeast species, including two that contain both Atg29/Atg31 and Atg101. Structural modeling and negative stain EM analysis indicated that budding yeast species with Atg101 exhibit a rod-shaped Atg17. Additionally, we found that the Atg13 HORMA domain of S. pombe may possess a stabilizing cap, suggesting an alternative function for Atg101. Collectively, our findings delineate the potential evolutionary trajectories of the Atg1 complex in yeast. Abbreviations: ATG, autophagy-related; BLAST, basic local alignment search tool; C-Mad2, closed Mad2; EAT, Early Autophagy Targeting/Tethering; EM, electron microscopy; His-MBP, histidine-maltose binding protein; HORMA, Hop1, Rev7, and Mad2; IDR, intrinsically disordered region; O-Mad2, open Mad2; iTOL, Interactive Tree of Life; PAS, phagophore assembly site; PI3K, phosphatidylinositol 3-kinase; PMSF, phenylmethylsulfonyl fluoride; pTM, predicted template modeling; RMSD, root mean square deviation; TOR, target of rapamycin; TORC1, TOR complex 1.
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