Assembly and architecture of biogenesis of lysosome-related organelles complex-1 (BLOC-1).
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.
Department of Bio and Nano Chemistry, Kookmin University, Seoul 136-702, Korea.
Hyung Ho
HH
Lee
Daniel
D
Nemecek
Christina
C
Schindler
William J
WJ
Smith
Rodolfo
R
Ghirlando
Alasdair C
AC
Steven
Juan S
JS
Bonifacino
James H
JH
Hurley
D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D057446:Hydrodynamics; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D059748:Proteolysis; D014157:Transcription Factors / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D021122:Protein Subunits; D014157:Transcription Factors; C060759:enhancer-binding protein AP-3