Molecular basis of autophagosome maturation revealed by the structures of ATG5 with its interacting

来源 :The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会 | 被引量 : 0次 | 上传用户:sparkman007
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  Autophagy is a conserved event as the bulky catabolic process that responds to nutrient homeostasis and extracellular stress signals in all eukaryotes.When autophagy is induced, a double-membrane structure, autophagosome, envelopes the cellular components and degrades those cargoes by fusion with a lysosome or vacuole.During this process, the ATG12-ATG5 conjugate requires 2 different binding partners, ATG16L1 for autophagosome elongation and TECPR1 for lysosomal fusion.In this study, the crystal structures of human ATG5 in complex with an N-terminal domain of ATG16L1 and internal AIR domain of TECPR1 were determined.Both binding partners exhibit a similar alpha-helical structure containing a conserved binding motif, AFIM, and its importance were further confirmed by biochemical and cell biological analyses.These results provide new insights into the molecular details of the autophagosome maturation process, from its elongation to its fusion with a lysosome.
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