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Crystal Structure and Versatile Functional Roles of the COP9 Signalosome Subunit 1Crystal Structure and Versatile Functional Roles of the COP9 Signalosome Subunit 1
Structural highlights
FunctionCSN1_ARATH Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes such as photomorphogenesis and auxin and jasmonate responses. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF. It is involved in repression of photomorphogenesis in darkness by regulating the activity of COP1-containing Ubl ligase complexes. The complex is also required for degradation of IAA6 by regulating the activity of the Ubl ligase SCF-TIR complex. In the complex, it plays a central role in CSN assembly.[1] [2] Publication Abstract from PubMedThe constitutive photomorphogenesis 9 (COP9) signalosome (CSN) plays key roles in many biological processes, such as repression of photomorphogenesis in plants and protein subcellular localization, DNA-damage response, and NF-kappaB activation in mammals. It is an evolutionarily conserved eight-protein complex with subunits CSN1 to CSN8 named following the descending order of molecular weights. Here, we report the crystal structure of the largest CSN subunit, CSN1 from Arabidopsis thaliana (atCSN1), which belongs to the Proteasome, COP9 signalosome, Initiation factor 3 (PCI) domain containing CSN subunit family, at 2.7 A resolution. In contrast to previous predictions and distinct from the PCI-containing 26S proteasome regulatory particle subunit Rpn6 structure, the atCSN1 structure reveals an overall globular fold, with four domains consisting of helical repeat-I, linker helix, helical repeat-II, and the C-terminal PCI domain. Our small-angle X-ray scattering envelope of the CSN1-CSN7 complex agrees with the EM structure of the CSN alone (apo-CSN) and suggests that the PCI end of each molecule may mediate the interaction. Fitting of the CSN1 structure into the CSN-Skp1-Cul1-Fbox (SCF) EM structure shows that the PCI domain of CSN1 situates at the hub of the CSN for interaction with several other subunits whereas the linker helix and helical repeat-II of CSN1 contacts SCF using a conserved surface patch. Furthermore, we show that, in human, the C-terminal tail of CSN1, a segment not included in our crystal structure, interacts with IkappaBalpha in the NF-kappaB pathway. Therefore, the CSN complex uses multiple mechanisms to hinder NF-kappaB activation, a principle likely to hold true for its regulation of many other targets and pathways. Crystal structure and versatile functional roles of the COP9 signalosome subunit 1.,Lee JH, Yi L, Li J, Schweitzer K, Borgmann M, Naumann M, Wu H Proc Natl Acad Sci U S A. 2013 Jul 1. PMID:23818606[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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