5BXL

Yeast 20S proteasome beta2-G170A mutant

Summary for 5BXL

• Entry DOI: 10.2210/pdb5bxl/pdb
• Related: 1RYP
• Descriptor: Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (17 entities in total)
• Functional Keywords: hydrolase, immunodeficiency, proteasome, mutant, assembly defect
• Biological source: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast); More
• Total number of polymer chains: 28
• Total formula weight: 731368.48

Authors

Huber, E.M.,Groll, M. (deposition date: 2015-06-09, release date: 2016-06-15, Last modification date: 2024-01-10)

Primary citation

Treise, I.,Huber, E.M.,Klein-Rodewald, T.,Heinemeyer, W.,Grassmann, S.A.,Basler, M.,Adler, T.,Rathkolb, B.,Helming, L.,Andres, C.,Klaften, M.,Landbrecht, C.,Wieland, T.,Strom, T.M.,McCoy, K.D.,Macpherson, A.J.,Wolf, E.,Groettrup, M.,Ollert, M.,Neff, F.,Gailus-Durner, V.,Fuchs, H.,Hrabe de Angelis, M.,Groll, M.,Busch, D.H.
Defective immuno- and thymoproteasome assembly causes severe immunodeficiency.
Sci Rep, 8:5975-5975, 2018

PubMed Abstract: 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 β2i-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 β2i 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 β1i (LMP2) and β5i (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.

PubMed: 29654304
DOI: 10.1038/s41598-018-24199-0

Experimental method

X-RAY DIFFRACTION (2.8 Å)