Xuan Ge, Jinqi Ren, Kewei Gu, Weibin Gong, Kang Shen, Wei Feng
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The structure and assembly of the hetero-octameric BLOC-one-related complex
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.
期刊介绍：
Structure aims to publish papers of exceptional interest in the field of structural biology. The journal strives to be essential reading for structural biologists, as well as biologists and biochemists that are interested in macromolecular structure and function. Structure strongly encourages the submission of manuscripts that present structural and molecular insights into biological function and mechanism. Other reports that address fundamental questions in structural biology, such as structure-based examinations of protein evolution, folding, and/or design, will also be considered. We will consider the application of any method, experimental or computational, at high or low resolution, to conduct structural investigations, as long as the method is appropriate for the biological, functional, and mechanistic question(s) being addressed. Likewise, reports describing single-molecule analysis of biological mechanisms are welcome.
In general, the editors encourage submission of experimental structural studies that are enriched by an analysis of structure-activity relationships and will not consider studies that solely report structural information unless the structure or analysis is of exceptional and broad interest. Studies reporting only homology models, de novo models, or molecular dynamics simulations are also discouraged unless the models are informed by or validated by novel experimental data; rationalization of a large body of existing experimental evidence and making testable predictions based on a model or simulation is often not considered sufficient.
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