The primary structures of four subunits of the human, high-molecular-weight proteinase, macropain (proteasome), are distinct but homologous.
Macropain (proteasome) is a high-molecular-weight proteinase complex composed of at least 13 electrophoretically distinct subunits. Previous work, including peptide mapping and limited amino acid sequencing, suggested that most of the subunits belong to an evolutionarily related group of different gene products (Lee et al. (1990) Biochim. Biophys. Acta. 1037, 178-185). In order to define the extent and pattern of subunit relatedness, and to determine the structural basis for possible similarities and differences in subunit functions, we are deducing the primary structures of macropain subunits by cDNA cloning and DNA sequence analysis. We report here the primary structures of four subunits. The data clearly demonstrate that the proteins represent different, but homologous gene products. Surprisingly, no evidence for homology with any other protein, including proteinases, was obtained. These results suggest that macropain is comprised of a previously unidentified family of evolutionarily related polypeptides. Because biochemical data indicate that macropain contains several different proteinase activities, the current results raise the possibility that the macropain complex is composed of a group of novel proteinases, distinct from those of other structurally identifiable proteinase families.
DeMartino
G N
GN
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235.
Orth
K
K
McCullough
M L
ML
Lee
L W
LW
Munn
T Z
TZ
Moomaw
C R
CR
Dawson
P A
PA
Slaughter
C A
CA
D000595:Amino Acid Sequence; D001483:Base Sequence; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics; D004247:DNA / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics; D046988:Proteasome Endopeptidase Complex; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid
D009097:Multienzyme Complexes; D012333:RNA, Messenger; D004247:DNA; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex