The subunits MECL-1 and LMP2 are mutually required for incorporation into the 20S proteasome.
Processing of antigens for presentation by major histocompatibility complex (MHC) class I molecules requires the activity of the proteasome. The 20S proteasome complex is composed of 14 different subunits, 2 of which can be substituted by the interferon gamma (IFN-gamma)-inducible and MHC-encoded subunits LMP2 and LMP7 (low molecular mass poylpeptides 2 and 7). A third subunit, MECL-1, is inducible by IFN-gamma but is encoded outside the MHC. Here we show by cotransfection experiments that the incorporation of MECL-1 into the 20S proteasome is directly dependent on the expression of LMP2 but independent of LMP7. Conversely, the uptake of LMP2 is strongly enhanced by MECL-1 expression. The expression of MECL-1 caused a replacement of the homologous subunit Z in the 20S proteasome complex. LMP2 is required for MECL-1 incorporation at the level of proteasome precursor formation that guarantees the concerted incorporation of two IFN-gamma-inducible proteasome subunits encoded inside and outside the MHC. The obligatory coincorporation of MECL-1 and LMP2 is an important parameter for the interpretation of results obtained with LMP2-deficient cell lines and mice as well as for the design of experiments addressing the function of MECL-1 in antigen presentation.
Groettrup
M
M
Institute for Biochemistry, Medical Faculty (Charité), Humboldt University, Monbijoustrasse 2a, D-10117 Berlin, Germany.
Standera
S
S
Stohwasser
R
R
Kloetzel
P M
PM
D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics / Q000276:immunology; D051379:Mice; D009097:Multienzyme Complexes / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D009097:Multienzyme Complexes; D011506:Proteins; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex; C490920:Psmb10 protein, mouse