4r14
From Proteopedia
Crystal structure of human CSN6 MPN domain
Structural highlights
Function[CSN6_HUMAN] Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. 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-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. Has some glucocorticoid receptor-responsive activity. Stabilizes RFWD2/COP1 through reducing RFWD2 auto-ubiquitination and decelerating RFWD2 turnover rate, hence regulates the ubiquitination of RFWD2 targets.[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe mammalian COP9 signalosome is an eight-subunit (CSN1-CSN8) complex that plays essential roles in multiple cellular and physiological processes. CSN5 and CSN6 are the only two MPN (Mpr1-Pad1-N-terminal) domain-containing subunits in the complex. Unlike the CSN5 MPN domain, CSN6 lacks a metal-binding site and isopeptidase activity. Here, we report the crystal structure of the human CSN6 MPN domain. Each CSN6 monomer contains nine beta sheets surrounded by three helices. Two forms of dimers are observed in the crystal structure. Interestingly, a domain swapping of beta8 and beta9 strands occurs between two neighboring monomers to complete a typical MPN fold. Analyses of the pseudo metal-binding motif in CSN6 suggest that the loss of two key histidine residues may contribute to the lack of catalytic activity in CSN6. Comparing the MPN domain of our CSN6 with that in the CSN complex shows that apart from the different beta8-beta9 conformation, they have minor conformational differences at two insertion regions (Ins-1 and Ins-2). Besides, the interacting mode of CSN6-CSN6 in our structure is distinct from that of CSN5-CSN6 in the CSN complex structure. Moreover, the functional implications for Ins-1 and Ins-2 are discussed. Crystal structure of the human CSN6 MPN domain.,Ma XL, Xu M, Jiang T Biochem Biophys Res Commun. 2014 Sep 19. pii: S0006-291X(14)01662-3. doi:, 10.1016/j.bbrc.2014.09.046. PMID:25242525[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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