5bxn | pdb_00005bxn

Yeast 20S proteasome beta2-G170A mutant in complex with Bortezomib

spinqualitylabelsall models 5bxn, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5bxn is a 20 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: BO2, CL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PSA3_YEAST The proteasome degrades poly-ubiquitinated proteins in the cytoplasm and in the nucleus. It is essential for the regulated turnover of proteins and for the removal of misfolded proteins. The proteasome is a multicatalytic proteinase complex that is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. It has an ATP-dependent proteolytic activity. Publication Abstract from PubMed By N-ethyl-N-nitrosourea (ENU) mutagenesis, we generated the mutant mouse line TUB6 that is characterised by severe combined immunodeficiency (SCID) and systemic sterile autoinflammation in homozygotes, and a selective T cell defect in heterozygotes. The causative missense point mutation results in the single amino acid exchange G170W in multicatalytic endopeptidase complex subunit-1 (MECL-1), the beta2i-subunit of the immuno- and thymoproteasome. Yeast mutagenesis and crystallographic data suggest that the severe TUB6-phenotype compared to the MECL-1 knockout mouse is caused by structural changes in the C-terminal appendage of beta2i that prevent the biogenesis of immuno- and thymoproteasomes. Proteasomes are essential for cell survival, and defective proteasome assembly causes selective death of cells expressing the mutant MECL-1, leading to the severe immunological phenotype. In contrast to the immunosubunits beta1i (LMP2) and beta5i (LMP7), mutations in the gene encoding MECL-1 have not yet been assigned to human disorders. The TUB6 mutant mouse line exemplifies the involvement of MECL-1 in immunopathogenesis and provides the first mouse model for primary immuno- and thymoproteasome-associated immunodeficiency that may also be relevant in humans. Defective immuno- and thymoproteasome assembly causes severe immunodeficiency.,Treise I, Huber EM, Klein-Rodewald T, Heinemeyer W, Grassmann SA, Basler M, Adler T, Rathkolb B, Helming L, Andres C, Klaften M, Landbrecht C, Wieland T, Strom TM, McCoy KD, Macpherson AJ, Wolf E, Groettrup M, Ollert M, Neff F, Gailus-Durner V, Fuchs H, Hrabe de Angelis M, Groll M, Busch DH Sci Rep. 2018 Apr 13;8(1):5975. doi: 10.1038/s41598-018-24199-0. PMID:29654304 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Proteasome 3D structures

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