DOI: 10.1128/iai.70.12.7105-7113.2002. Functional Comparison of Serine Protease Autotransporters of <i>Enterobacteriaceae</i>

Functional Comparison of Serine Protease Autotransporters of Enterobacteriaceae

10.1128/iai.70.12.7105-7113.2002

Crossref journal-article

American Society for Microbiology

Infection and Immunity (235)

Abstract

ABSTRACT The plasmid-encoded toxin (Pet) of enteroaggregative Escherichia coli (EAEC) belongs to a family of high-molecular-weight serine protease autotransporters of Enterobacteriaceae (SPATEs) which also includes Pic from EAEC and Shigella flexneri , EspC from enteropathogenic E. coli , EspP from enterohemorrhagic E. coli , Sat from uropathogenic E. coli , Tsh from avian pathogenic E. coli , and SepA from S. flexneri . Phylogenetic analysis shows the SPATE proteins to represent a distinct subfamily of autotransporters with amino acid identities ranging from 35 to 55%, providing a powerful resource to direct structure-function studies. In this study, we show that these related proteins are proteases with divergent substrate specificities, suggesting different functions. The cleavage profile of oligopeptides was found to be unique for each SPATE protein. The SPATEs showed proteolytic activity for several substrates, namely mucin, pepsin, human coagulation factor V, and erythroid spectrin. The cleavage of spectrin has been hypothesized as the mechanism through which Pet induces cytopathic effects. However, whereas Pet, Sat, and EspC cleaved spectrin, only Pet and Sat elicited cytopathic effects; the remaining SPATEs did not cause any morphological changes to HEp-2 cell monolayers. EspC and Pet exhibited acid-dissociable binding to HEp-2 cells. However, Pet was more efficient at entering HEp-2 cells, suggesting a basis for the different abilities of these two proteases to damage cells. Our data suggest that, despite the homologies observed among these proteins, the SPATEs have different pathogenetic functions only partly dependent on their substrate specificities.

Bibliography

Dutta, P. R., Cappello, R., Navarro-GarciÌa, F., & Nataro, J. P. (2002). Functional Comparison of Serine Protease Autotransporters of Enterobacteriaceae. Infection and Immunity, 70(12), 7105â7113.

Authors 4

Pinaki R. Dutta (first)
Renato Cappello (additional)
Fernando Navarro-García (additional)
James P. Nataro (additional)

References 26 Referenced 157

Alberts B. D. Bray J. Lewis M. Raff K. Roberts and J. Watson. 1994. Molecular biology of the cell 3rd ed. Garland Publishing Inc. New York N.Y.
10.1111/j.1365-2958.1995.mmi_17010123.x
10.1099/00221287-144-7-1815
10.1016/0022-2836(69)90288-5
10.1046/j.1365-2958.1997.3871751.x
10.1046/j.1365-2958.1997.5141874.x
10.1128/IAI.66.7.3155-3163.1998
Fersht A. 1984. Enzyme structure and mechanism 2nd ed. W. H. Freeman and Company New York N.Y.
10.1074/jbc.M106913200
10.1046/j.1365-2958.2000.02110.x
10.1016/S0966-842X(00)01853-9
10.1128/IAI.67.11.5587-5596.1999
10.1128/IAI.69.3.1231-1243.2001
10.1093/bioinformatics/14.1.68
10.1128/iai.59.1.365-371.1991
10.1038/227680a0
10.1128/IAI.69.1.315-324.2001
10.1128/IAI.69.2.1053-1060.2001
10.1128/IAI.66.7.3149-3154.1998
10.1128/IAI.67.5.2184-2192.1999
10.1128/IAI.70.1.5-10.2002
10.1084/jem.188.6.1091
10.1128/iai.62.4.1369-1380.1994
10.1016/0076-6879(94)44004-2
10.1128/jb.178.22.6546-6554.1996
10.1128/IAI.68.10.5920-5927.2000

Dates

Type	When
Created	22 years, 9 months ago (Nov. 18, 2002, 6:04 p.m.)
Deposited	3 years, 6 months ago (March 4, 2022, 9:36 p.m.)
Indexed	1 month, 2 weeks ago (July 19, 2025, 11:54 p.m.)
Issued	22 years, 9 months ago (Dec. 1, 2002)
Published	22 years, 9 months ago (Dec. 1, 2002)
Published Print	22 years, 9 months ago (Dec. 1, 2002)

Funders 0

None

BibTeX

@article{Dutta_2002, title={Functional Comparison of Serine Protease Autotransporters of Enterobacteriaceae}, volume={70}, ISSN={1098-5522}, url={http://dx.doi.org/10.1128/iai.70.12.7105-7113.2002}, DOI={10.1128/iai.70.12.7105-7113.2002}, number={12}, journal={Infection and Immunity}, publisher={American Society for Microbiology}, author={Dutta, Pinaki R. and Cappello, Renato and Navarro-García, Fernando and Nataro, James P.}, year={2002}, month=dec, pages={7105–7113} }

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