Abstract
The COP9 signalosome (CSN) is a eukaryotic protein complex, which regulates a wide range of biological processes mainly through modulating the cullin ubiquitin E3 ligases in the ubiquitin-proteasome pathway. The CSN possesses a highly conserved deneddylase activity that centers at the JAMM motif of the Csn5 subunit but requires other subunits in a complex assembly. The classic CSN is composed of 8 subunits (Csn1–8), yet in several Ascomycota, the complex is smaller and lacks orthologs for a few CSN subunits, but nevertheless contains a conserved Csn5. This feature makes yeast a powerful model to determine the minimal assemblage required for deneddylation activity. Here we report, that Csi1, a diverged S. cerevisiae CSN subunit, displays significant homology with the carboxyl terminal domain of the canonical Csn6, but lacks the amino terminal MPN- domain. Through the comparative and experimental analyses of the budding yeast and the mammalian CSNs, we demonstrate that the MPN− domain of the canonical mouse Csn6 is not part of the CSN deneddylase core. We also show that the carboxyl domain of Csn6 has an indispensable role in maintaining the integrity of the CSN complex. The CSN complex assembled with the carboxyl fragment of Csn6, despite its lack of an MPN− domain, is fully active in deneddylation of cullins. We propose that the budding yeast Csi1 is a functional equivalent of the canonical Csn6, and thus the composition of the CSN across phyla is more conserved than hitherto appreciated.
Highlights
The COP9 signalosome (CSN) is an evolutionarily conserved protein complex with a canonical composition of eight subunits (Csn1–8) [1]
By analyzing the amino acid sequences, we found that the carboxyl-terminal domain of ScCsi1 shares homology with the C-terminal region of canonical Csn6 from multicellular organisms (Figure 1, 2A)
CSN6 is not found in a completed genomic database of several parasitic protists including Giardia intestinalis, possibly due to a comprehensive loss of genes involve in protein quality control, including CSN encoding genes [32]
Summary
The COP9 signalosome (CSN) is an evolutionarily conserved protein complex with a canonical composition of eight subunits (Csn1–8) [1]. The CSN belongs to a family of protein complexes known as the PCI complexes, which include the lid subcomplex of the 26S proteasome, the CSN, and the eukaryotic translation initiation factor-3 (eIF3) (Table 1, [8]). Members of this family play key roles in the regulation of protein life span from translation to degradation [8,9,10]. Subunits of these complexes share large structural elements such as PCI or MPN (Mpr1/Pad N-terminal) domains [11], and are arranged in a comparable architecture [12]
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