To characterize interaction between RUN and FYVE domain containing protein (RUFY1) and dynein-dynaction complex

Abstract

RUN and FVYE domain containing protein (RUFY1), recently reported as a regulator of Cation Independent Mannose 6 Phosphate Receptor (CI-M6PR) cargo sorting from recycling endosomes to Trans Golgi Network (TGN) which interacts with the Arl8b an Arf like GTP binding protein through their RUN domain and also interacts with the small GTP binding protein Rab14 through their Coiled-Coiled domain 3(CC3). It was known that RUFY1 interacts with the Light Intermediate Chain 1 (LIC1) of dynein-dynactin complex similar to a subset of activating dynein adaptors, which is important for CI-M6PR cargo retrieval from endosome to TGN. We used AlphaFold Colab to identify interacting residues between RUFY1 and LIC1 and also identified conserved residues between RUFY1 and other activating adaptors like BICD2, TRAK2 and HAP1 using protein sequence alignment. The present study helps in understanding the localization of these RUFY1 mutants and elucidating the significance of these mutants in binding with LIC1 subunit of dynein.