title: Symmetrical modularity of the COP9 signalosome complex suggests its multifunctionality.
abstract: The COP9 signalosome (CSN) is an eight-subunit protein complex that is found in all eukaryotes. Accumulating evidence indicates its diverse biological functions that are often linked to ubiquitin-mediated proteolysis. Here we applied an emerging mass spectrometry approach to gain insight into the structure of the CSN complex. Our results indicate that the catalytically active human complex, reconstituted in vitro, is composed of a single copy of each of the eight subunits. By forming a total of 35 subcomplexes, we are able to build a comprehensive interaction map that shows two symmetrical modules, Csn1/2/3/8 and Csn4/5/6/7, connected by interactions between Csn1-Csn6. Overall the stable modules and multiple subcomplexes observed here are in agreement with the "mini-CSN" complexes reported previously. This suggests that the propensity of the CSN complex to change and adapt its subunit composition might underlie its ability to perform multiple functions in vivo.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK.
authors.forename: Michal
authors.initials: M
authors.lastname: Sharon
authors.forename: Haibin
authors.initials: H
authors.lastname: Mao
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Boeri Erba
authors.forename: Elaine
authors.initials: E
authors.lastname: Stephens
authors.forename: Ning
authors.initials: N
authors.lastname: Zheng
authors.forename: Carol V
authors.initials: CV
authors.lastname: Robinson
mesh_terms: D000075686:COP9 Signalosome Complex; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000737:chemistry / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D046912:Multiprotein Complexes; D010447:Peptide Hydrolases; D000075686:COP9 Signalosome Complex