MHC-linked low-molecular mass polypeptide subunits define distinct subsets of proteasomes. Implications for divergent function among distinct proteasome subsets.
Proteasomes are 650-kDa, multisubunit endopeptidases that might be involved in the MHC class I Ag processing pathway. We demonstrate the existence of multiple structurally distinct subsets of proteasomes. Distinct forms of proteasomes share a hypothetical core to which unique subunits are added. One of these subsets, LMP2+ proteasome, contains the product of the MHC-linked Lmp-2 gene, and can be distinguished serologically and structurally from other proteasome subsets. The expression of LMP2+ and LMP2- proteasomes is variable among cell lines of different tissue types, and their relative abundance and subunit composition are regulated by IFN-gamma. LMP2+ proteasomes comprise 0 to 74% of total cellular proteasomes. Both LMP2+ and LMP2- proteasomes are proteolytically active. We suggest proteasome function might be regulated by subunit composition, and some, or all proteasome subsets, might participate in the production or delivery of peptides to MHC class I molecules. Both LMP2+ and LMP2- subsets can be further subdivided on the basis of the presence or absence of other unique subunits. Implications of the existence of structurally distinct forms of proteasomes in different tissue types is discussed.
Brown
M G
MG
Department of Microbiology and Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0678.
Driscoll
J
J
Monaco
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D005805:Genes, MHC Class I; D008285:Major Histocompatibility Complex; D051379:Mice; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism; D013379:Substrate Specificity
D009097:Multienzyme Complexes; D009842:Oligopeptides; D011506:Proteins; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex