Immunoproteasome assembly: cooperative incorporation of interferon gamma (IFN-gamma)-inducible subunits.
LMP2, LMP7, and MECL are interferon gamma-inducible catalytic subunits of vertebrate 20S proteasomes, which can replace constitutive catalytic subunits (delta, X, and Z, respectively) during proteasome biogenesis. We demonstrate that MECL requires LMP2 for efficient incorporation into preproteasomes, and preproteasomes containing LMP2 and MECL require LMP7 for efficient maturation. The latter effect depends on the presequence of LMP7, but not on LMP7 catalytic activity. This cooperative mechanism favors the assembly of homogeneous "immunoproteasomes" containing all three inducible subunits, suggesting that these subunits act in concert to enhance proteasomal generation of major histocompatibility complex class I-binding peptides.
Griffin
T A
TA
William S. Rowe Division of Rheumatology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Nandi
D
D
Cruz
M
M
Fehling
H J
HJ
Kaer
L V
LV
Monaco
J J
JJ
Colbert
R A
RA
D000818:Animals; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D004792:Enzyme Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D014162:Transfection
D004792:Enzyme Precursors; D009097:Multienzyme Complexes; D011506:Proteins; C071313:LMP-2 protein; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; C098948:PSMB10 protein, human; D046988:Proteasome Endopeptidase Complex; C490920:Psmb10 protein, mouse