Assembly and architecture of biogenesis of lysosome-related organelles complex-1 (BLOC-1)

J Biol Chem. 2012 Feb 17;287(8):5882-90. doi: 10.1074/jbc.M111.325746. Epub 2011 Dec 27.

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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • DNA-Binding Proteins / metabolism
  • Humans
  • Hydrodynamics
  • Protein Multimerization*
  • Protein Stability
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Proteolysis
  • Transcription Factors / metabolism

Substances

  • Carrier Proteins
  • DNA-Binding Proteins
  • Protein Subunits
  • Transcription Factors
  • enhancer-binding protein AP-3