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Calcium Regulates the Activity and Structural Stability of Tpr, a Bacterial Calpain-like Peptidase.

Staniec, Dominika; Ksiazek, Miroslaw; Thøgersen, Ida B; Enghild, Jan J; Sroka, Aneta; Bryzek, Danuta; Bogyo, Matthew; Abrahamson, Magnus LU and Potempa, Jan (2015) In Journal of Biological Chemistry 290(45). p.27248-27260
Abstract
Porphyromonas gingivalis is a peptide-fermenting asaccharolytic periodontal pathogen. Its genome contains several genes encoding cysteine peptidases other than gingipains. One of these genes (PG1055) encodes a protein called Tpr (thiol protease), which has sequence similarity to cysteine peptidases of the papain and calpain families. In this study, we biochemically characterize Tpr. We found that the 55 kDa Tpr inactive zymogen proteolytically processes itself into active forms of 48 kDa, 37 kDa, and 33 kDa via sequential truncations at the N-terminus. These processed molecular forms of Tpr are associated with the bacterial outer membrane, where they are likely responsible for the generation of metabolic peptides required for survival of... (More)
Porphyromonas gingivalis is a peptide-fermenting asaccharolytic periodontal pathogen. Its genome contains several genes encoding cysteine peptidases other than gingipains. One of these genes (PG1055) encodes a protein called Tpr (thiol protease), which has sequence similarity to cysteine peptidases of the papain and calpain families. In this study, we biochemically characterize Tpr. We found that the 55 kDa Tpr inactive zymogen proteolytically processes itself into active forms of 48 kDa, 37 kDa, and 33 kDa via sequential truncations at the N-terminus. These processed molecular forms of Tpr are associated with the bacterial outer membrane, where they are likely responsible for the generation of metabolic peptides required for survival of the pathogen. Both autoprocessing and activity were dependent on calcium concentrations greater than 1 mM, consistent with the protein's activity within the intestinal and inflammatory milieus. Calcium also stabilized the Tpr structure and rendered the protein fully resistant to proteolytic degradation by gingipains. Together, our findings suggest that Tpr is an example of a bacterial calpain, a calcium-responsive peptidase that may generate substrates required for the peptide-fermenting metabolism of P. gingivalis. Aside from nutrient generation, Tpr may also be involved in evasion of host immune response through degradation of the antimicrobial peptide LL-37 and complement proteins C3, C4 and C5. Taken together, these results indicate that Tpr likely represents an important pathogenesis factor for P. gingivalis. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
290
issue
45
pages
27248 - 27260
publisher
ASBMB
external identifiers
  • pmid:26385924
  • wos:000364794000033
  • scopus:84946761891
ISSN
1083-351X
DOI
10.1074/jbc.M115.648782
language
English
LU publication?
yes
id
444d3fea-8f6e-433a-ac5c-cad585dc3600 (old id 8035865)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/26385924?dopt=Abstract
date added to LUP
2015-10-03 18:43:34
date last changed
2017-07-23 03:28:33
@article{444d3fea-8f6e-433a-ac5c-cad585dc3600,
  abstract     = {Porphyromonas gingivalis is a peptide-fermenting asaccharolytic periodontal pathogen. Its genome contains several genes encoding cysteine peptidases other than gingipains. One of these genes (PG1055) encodes a protein called Tpr (thiol protease), which has sequence similarity to cysteine peptidases of the papain and calpain families. In this study, we biochemically characterize Tpr. We found that the 55 kDa Tpr inactive zymogen proteolytically processes itself into active forms of 48 kDa, 37 kDa, and 33 kDa via sequential truncations at the N-terminus. These processed molecular forms of Tpr are associated with the bacterial outer membrane, where they are likely responsible for the generation of metabolic peptides required for survival of the pathogen. Both autoprocessing and activity were dependent on calcium concentrations greater than 1 mM, consistent with the protein's activity within the intestinal and inflammatory milieus. Calcium also stabilized the Tpr structure and rendered the protein fully resistant to proteolytic degradation by gingipains. Together, our findings suggest that Tpr is an example of a bacterial calpain, a calcium-responsive peptidase that may generate substrates required for the peptide-fermenting metabolism of P. gingivalis. Aside from nutrient generation, Tpr may also be involved in evasion of host immune response through degradation of the antimicrobial peptide LL-37 and complement proteins C3, C4 and C5. Taken together, these results indicate that Tpr likely represents an important pathogenesis factor for P. gingivalis.},
  author       = {Staniec, Dominika and Ksiazek, Miroslaw and Thøgersen, Ida B and Enghild, Jan J and Sroka, Aneta and Bryzek, Danuta and Bogyo, Matthew and Abrahamson, Magnus and Potempa, Jan},
  issn         = {1083-351X},
  language     = {eng},
  number       = {45},
  pages        = {27248--27260},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Calcium Regulates the Activity and Structural Stability of Tpr, a Bacterial Calpain-like Peptidase.},
  url          = {http://dx.doi.org/10.1074/jbc.M115.648782},
  volume       = {290},
  year         = {2015},
}