A structural model of 20S immunoproteasomes: effect of LMP2 codon 60 polymorphism on expression, activity, intracellular localisation and insight into the regulatory mechanisms

Biological Chemistry - Tập 387 Số 4 - Trang 417-429 - 2006
Michele Mishto1, Aurelia Santoro2, Elena Bellavista3, Richard B. Sessions4, Kathrin Textoris‐Taube5, Fabrizio Dal Piaz3, Géraldine Carrard6, Katia Forti4, Stefano Salvioli2, Bertrand Friguet6, Peter M. Kloetzel5, A. Jennifer Rivett4, Claudio Franceschi7
1Department of Experimental Pathology, University of Bologna, via S. Giacomo 14, I-40126 Bologna, Italy. [email protected]
2Interdepartmental Ctr. for Studs. on Biophysics, Bioinformatics and Biocomplexity 'L. Galvani' (CIG)
3University of Bologna,
4University of Bristol
5Humboldt Universitát zu Berlin
6 Université Paris 7
7Istituto Scienze Neurologiche

Tóm tắt

AbstractThe immunoproteasome subunit low molecular weight protein 2 (LMP2) codon 60 polymorphism has been associated with autoimmune diseases. It has also been demonstrated to influence susceptibility to TNF-α-induced apoptosis in blood cells and proteasome activity in aged human brain. In the present study, anin silicomodel of immunoproteasome was used to examine the effect of the R60H polymorphism in the LMP2 subunit. The investigation of immunoproteasome expression, activity and intracellular localisation in anin vitrocellular model, namely lymphoblastoid cell lines, showed no major variations in functionality and amount, while a significant difference in antibody affinity was apparent. These data were integrated with previous results obtained in different tissues and combined with a structural model of the LMP2 polymorphism. Accordingly, we identified three prospective mechanisms that could explain the biological data for the polymorphism, such as modulation of the binding affinity of a putative non-catalytic modifier site on the external surface of the immunoproteasome core, or the modification of any channel between α and β rings.

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Thông tin xuất bản

Biological Chemistry

Tập 387 Số 4

417-429

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