Fig. 2: SNX17 CT tail is sequestered by FERM domain and displaced by cargo binding.

a Left: Overlay of an AlphaFold model of FL SNX17 with crystal structures of the SNX17 FERM domain bound to cargo peptides. The NxxY/F motifs are highlighted in red. Right: Cartoon representation show how cargo binding displaces the sequestered CT tail to promote Retriever binding. b Cartoon representation of SNX17 and cargo constructs used. c–g Coomassie blue-stained SDS PAGE gels showing in vitro pull-down under the indicated conditions. c shows GST-SNX17 CT tail pulling down indicated SNX17 constructs in the presence of 0.6 µM KRIT1 cargo peptide or 200 µM PI(3)P diC4, a short chain, soluble PI(3)P analog. d shows GST-SNX17 CT tail mutants pulling down the SNX17 FERM domain. e shows GST-SNX17 CT tails pulling down the FERM domain in the presence of increasing concentrations of Retriever. f shows GST-SNX17 CT tail pulling down Retriever in the presence of FERM domain and/or increasing concentrations of cargo peptide. g shows His₆-tagged Retriever on TALON beads pulling down untagged FL SNX17 in the presence of 6 µM cargo peptide or 200 µM PI(3)P diC4. Representative results from at least two independent experiments are shown for each pull-down. Source data for c–g are provided as a Source Data file.