PRE2, highly homologous to the human major histocompatibility complex-linked RING10 gene, codes for a yeast proteasome subunit necessary for chrymotryptic activity and degradation of ubiquitinated proteins.
We have cloned the yeast PRE2 gene by complementation of pre2 mutants, which are defective in the chymotrypsin-like activity of the 20 S proteasome (multicatalytic-multifunctional proteinase complex). The PRE2 gene, a beta-type member of the proteasomal gene family, is essential for life and codes for a 287-amino acid proteasomal subunit with a predicted molecular mass of 31.6 kDa. Missense mutations in two pre2 mutant alleles were identified. They led to enhanced sensitivity of yeast cells against stress. At the same time, pre2 mutants accumulated ubiquitinated proteins. The Pre2 protein shows striking homology to the human Ring10 protein (60% identity excluding the 70 amino-terminal residues), which is encoded in the major histocompatibility complex class II region. It represents a component of the low molecular mass polypeptide complex, previously shown to be a special type of the 20 S proteasome. The low molecular mass polypeptide complex is assumed to be involved in antigen presentation, generating peptides from cytosolic protein antigens, which are subsequently presented to cytotoxic T-lymphocytes on the cell surface. The high homology of Pre2 to Ring10 implies the hypothesis that Ring10 is a subunit of the low molecular mass polypeptide complex central in its chymotryptic activity. One might further suggest that replacement of constitutive proteasomal components by functionally related major histocompatibility complex-linked low molecular mass polypeptides, as is Ring10, adapts mammalian proteasomes for functions in the immune response.
Institut für Biochemie, Universität Stuttgart, Germany.
W
W
Heinemeyer
A
A
Gruhler
V
V
Möhrle
Y
Y
Mahé
D H
DH
Wolf
D000595:Amino Acid Sequence; D001483:Base Sequence; D002918:Chymotrypsin / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000235:genetics*; D004271:DNA, Fungal; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000235:genetics*; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D014452:Ubiquitins / Q000378:metabolism*
D004271:DNA, Fungal; D005656:Fungal Proteins; D009097:Multienzyme Complexes; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; D014452:Ubiquitins; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; C080044:PRE2 protein, S cerevisiae; D046988:Proteasome Endopeptidase Complex