Structural insights into the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3.
The evolutionary conserved COP9 signalosome (CSN), a large multisubunit complex, plays a central role in regulating ubiquitination and cell signaling. Here we report recombinant insect cell expression and two-step purification of human CSN and demonstrate its functional assembly. We further obtain a three-dimensional structure of both native and recombinant CSN using electron microscopy and single particle analysis. Antibody labeling of CSN5 and segmentation of the structure suggest a likely subunit distribution and the architecture of its helical repeat subunits is revealed. We compare the structure of CSN with its homologous complexes, the 26S proteasome lid and eIF3, and propose a conserved architecture implying similar assembly pathways and/or conserved substrate interaction modes.
Enchev
Radoslav I
RI
Section of Structural Biology, The Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London SW3 6JB, UK.
Schreiber
Anne
A
Beuron
Fabienne
F
Morris
Edward P
EP
D000075686:COP9 Signalosome Complex; D003001:Cloning, Molecular; D004912:Erythrocytes / Q000166:cytology; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D008854:Microscopy, Electron / Q000379:methods; D008958:Models, Molecular; D008968:Molecular Conformation; D046912:Multiprotein Complexes / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000737:chemistry*; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D015398:Signal Transduction
D039621:Eukaryotic Initiation Factor-3; D047908:Intracellular Signaling Peptides and Proteins; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease