Characterization of a multicopy family of genes encoding a surface-expressed serine endoprotease in rat Pneumocystis carinii.
A unique family of genes encoding serine endoproteases related to the Saccharomyces cerevisiae serine endoprotease kexin was identified in Pneumocystis carinii. Unlike previously described serine endoprotease genes that are single copies, multiple copies of the P. carinii serine endoprotease are distributed throughout the genome. The proteins predicted by these variant genes demonstrate sequence variability, but they retain the conserved active sites associated with endoprotease activity. The serine endoprotease was localized to the organism surface by immunohistochemical and immunofluorescence studies and to the electron lucent layer of the cyst wall by immunoelectron microscopy. The findings of multiple copies of the serine endoprotease gene in the P. carinii genome, and its localization to the cell surface, suggest that this protease plays an important role in the biology of P. carinii and that antigenic variation of the surface-expressed serine endoprotease may be a strategy for immune evasion. P. carinii serine endoprotease provides a novel target for chemotherapeutic and immune-based approaches to the treatment of P. carinii pneumonia.
Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1662, USA.
D A
DA
Russian
V
V
Andrawis-Sorial
M P
MP
Goheen
J C
JC
Edman
P
P
Vogel
R E
RE
Turner
D L
DL
Klivington
C W
CW
Angus
J A
JA
Kovacs
D000595:Amino Acid Sequence; D000818:Animals; D000940:Antigenic Variation; D005289:Ferrets / Q000382:microbiology; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D005800:Genes, Fungal; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D005810:Multigene Family; D011010:Pneumocystis / Q000235:genetics* / Q000276:immunology; D043484:Proprotein Convertases; D051381:Rats; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012697:Serine Endopeptidases / Q000096:biosynthesis / Q000235:genetics* / Q000276:immunology; D013381:Subtilisins / Q000235:genetics
D005656:Fungal Proteins; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D013381:Subtilisins; C058751:KEX2 protein, S cerevisiae