BORC (BLOC-one-related complex) is a hetero-octameric complex, consisting of eight coiled-coil proteins (BORCS1-8). BORC controls lysosomal and synaptic vesicle transport and positioning by recruiting ARL8. The structural mechanisms underlying BORC assembly and ARL8 activation remain unclear. Here, we reconstitute and construct the structural model of this hetero-octameric complex. We find that BORC adopts an extended, rod-like structure made of coiled coils. Two hemicomplexes, each containing four subunits, are joined end-to-end to form the holocomplex. Within each hemicomplex, BORCS1/4/6/8 or BORCS2/3/5/7 assembles into similar helical bundles. We further study how BORC is built and discover a hierarchical assembly process in which BORCS1/2/3/5 forms the core scaffold and recruits other subunits. Mutations in the inter-hemicomplex interfaces result in two hemicomplexes. The association of ARL8 may require the proper assembly of BORC and is primarily mediated by BORCS5. These results provide guidance for further understanding of the biology of BORC.
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