Structural Insights into Autophagy in the AlphaFold Era

Abstract

Autophagy, a lysosomal intracellular degradation system, is characterized by the de novo biogenesis of autophagosomes. This biogenesis is mediated by approximately 20 core Atg proteins, exhibiting a high degree of conservation from yeast to humans. Over the preceding two decades, the structural biology of autophagy has been investigated predominantly through X-ray crystallography, NMR spectroscopy, and, more recently, cryo-electron microscopy, collectively contributing to the elucidation of the structural basis of core Atg proteins. The recent introduction of AlphaFold has significantly improved the precision of structure prediction and is transforming structural biology research. In this review, we aim to synthesize the structural basis of the operational mechanisms of the core Atg proteins, employing structures predicted by AlphaFold, and to discuss the molecular mechanisms that drive autophagosome biogenesis.