Accessory Interaction Motifs in the Atg19 Cargo Receptor Enable Strong Binding to the Clustered Ubiquitin-related Atg8 Protein*

نویسندگان

  • Christine Abert
  • Georg Kontaxis
  • Sascha Martens
چکیده

Selective autophagy contributes to cellular homeostasis by delivering harmful material into the lysosomal system for degradation via vesicular intermediates referred to as autophagosomes. The cytoplasm-to-vacuole targeting pathway is a variant of selective autophagy in Saccharomyces cerevisiae during which hydrolases such as prApe1 are transported into the vacuole. In general, selectivity is achieved by autophagic cargo receptors that link the cargo to autophagosomal membranes because of their ability to simultaneously interact with the cargo and Atg8 proteins that coat the membrane. The Atg19 receptor contains multiple Atg8 interaction sites in its C terminus in addition to a canonical Atg8-interacting LC3-interacting region (LIR, with LC3 being a homolog of Atg8) motif, but their mode of interaction with Atg8 is unclear. Here we show, using a combination of NMR, microscopy-based interaction assays, and prApe1 processing experiments, that two additional sites interact with Atg8 in a LIR-like and thus mutually exclusive manner. We term these motifs accessory LIR motifs because their affinities are lower than that of the canonical LIR motif. Thus, one Atg19 molecule has the ability to interact with multiple Atg8 proteins simultaneously, resulting in a high-avidity interaction that may confer specific binding to the Atg8-coated autophagosomal membrane on which Atg8 is concentrated.

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عنوان ژورنال:

دوره 291  شماره 

صفحات  -

تاریخ انتشار 2016