Abstract
BLOC-1 (biogenesis of lysosome-related organelles complex-1) is critical for melanosome biogenesis and has also been implicated in neurological function and disease. We show that BLOC-1 is an elongated complex that contains one copy each of the eight subunits pallidin, Cappuccino, dysbindin, Snapin, Muted, BLOS1, BLOS2, and BLOS3. The complex appears as a linear chain of eight globular domains, ∼300 Å long and ∼30 Å in diameter. The individual domains are flexibly connected such that the linear chain undergoes bending by as much as 45°. Two stable subcomplexes were defined, pallidin-Cappuccino-BLOS1 and dysbindin-Snapin-BLOS2. Both subcomplexes are 1:1:1 heterotrimers that form extended structures as indicated by their hydrodynamic properties. The two subcomplexes appear to constitute flexible units within the larger BLOC-1 chain, an arrangement conducive to simultaneous interactions with multiple BLOC-1 partners in the course of tubular endosome biogenesis and sorting.
Highlights
The BLOC-1 complex is critical for biogenesis of lysosome-related organelles
We show that BLOC-1 is an elongated complex that contains one copy each of the eight subunits pallidin, Cappuccino, dysbindin, Snapin, Muted, BLOS1, BLOS2, and BLOS3
We found that the trio pallidin, Cappuccino, and BLOS1 and another trio, dysbindin, Snapin, and BLOS2, form elongated subcomplexes of 1:1:1 stoichiometry
Summary
The BLOC-1 complex is critical for biogenesis of lysosome-related organelles. Results: BLOC-1 is elongated, bends by up to 45o, and contains two heterotrimeric subcomplexes. We show that BLOC-1 is an elongated complex that contains one copy each of the eight subunits pallidin, Cappuccino, dysbindin, Snapin, Muted, BLOS1, BLOS2, and BLOS3. BLOC-1 contains eight subunits: dysbindin [3,4,5,6], Cappuccino [7, 8], pallidin (9 –11), Muted [11], Snapin [12, 13], and BLOS1, BLOS2, and BLOS3 [13, 14]. We found that the trio pallidin, Cappuccino, and BLOS1 and another trio, dysbindin, Snapin, and BLOS2, form elongated subcomplexes of 1:1:1 stoichiometry The regions of these six subunits responsible for core interactions in the subcomplexes were mapped. Taking these data together with modeling of the coiled coils and hydrodynamic analysis, we developed a low resolution model of the architecture of the core of BLOC-1
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