Biomaterial Database

Crystal structure of the human CSN6 MPN domain. 2014

Xiao-li Ma, and Min Xu, and Tao Jiang

National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, 19A Yuquan Road, Shijingshan District, Beijing 100039, China.

The 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 β sheets surrounded by three helices. Two forms of dimers are observed in the crystal structure. Interestingly, a domain swapping of β8 and β9 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 β8-β9 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.

UI	MeSH Term	Description	Entries
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D010446	Peptide Fragments	Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.	Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010447	Peptide Hydrolases	Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES.	Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, Peptide
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000075686	COP9 Signalosome Complex	A multiprotein complex that functions as a peptide hydrolase, or isopeptidase to cleave NEDD8 PROTEIN from the CULLIN and UBIQUITIN-PROTEIN LIGASES, controlling the activity of the ligases. It is highly conserved in eukaryotes and typically consists of 8 subunits (CSN 1-8 proteins). The COP9 signalosome was originally identified in plants, where it controls gene transcription in response to light.	COP9 Signalosome (CSN),COP9 Signalosome Subunit 1,COP9 Signalosome Subunit 2,COP9 Signalosome Subunit 3,COP9 Signalosome Subunit 4,COP9 Signalosome Subunit 5,COP9 Signalosome Subunit 6,COP9 Signalosome Subunit 7A,COP9 Signalosome Subunit 7B,COP9 Signalosome Subunit 8,COP9 Signalsome,Constitutive Photomorphogenesis 9 Signalosome,Constitutive Photomorphogenesis 9 Signalsome,FUSCA Protein 11,G Protein Pathway Suppressor 1,Sgn3,Signalosome Subunit 3,Signalosome Complex, COP9,Signalsome, COP9,Subunit 3, Signalosome
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001665	Binding Sites	The parts of a macromolecule that directly participate in its specific combination with another molecule.	Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D017386	Sequence Homology, Amino Acid	The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.	Homologous Sequences, Amino Acid,Amino Acid Sequence Homology,Homologs, Amino Acid Sequence,Homologs, Protein Sequence,Homology, Protein Sequence,Protein Sequence Homologs,Protein Sequence Homology,Sequence Homology, Protein,Homolog, Protein Sequence,Homologies, Protein Sequence,Protein Sequence Homolog,Protein Sequence Homologies,Sequence Homolog, Protein,Sequence Homologies, Protein,Sequence Homologs, Protein
D017433	Protein Structure, Secondary	The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which align to form BETA-SHEETS), or other types of coils. This is the first folding level of protein conformation.	Secondary Protein Structure,Protein Structures, Secondary,Secondary Protein Structures,Structure, Secondary Protein,Structures, Secondary Protein