BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
권호 표지
DOI QR코드

DOI QR Code

Structure and Function of HtrA Family Proteins, the Key Players in Protein Quality Control

  • Kim, Dong-Young (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine) ;
  • Kim, Kyeong-Kyu (Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine)
  • Published : 2005.05.31
Download PDF
⟨ Previous Next ⟩

Abstract

High temperature requirement A (HtrA) and its homologues constitute the HtrA familiy proteins, a group of heat shock-induced serine proteases. Bacterial HtrA proteins perform crucial functions with regard to protein quality control in the periplasmic space, functioning as both molecular chaperones and proteases. In contrast to other bacterial quality control proteins, including ClpXP, ClpAP, and HslUV, HtrA proteins contain no regulatory components or ATP binding domains. Thus, they are commonly referred to as ATP-independent chaperone proteases. Whereas the function of ATP-dependent chaperone-proteases is regulated by ATP hydrolysis, HtrA exhibits a PDZ domain and a temperature-dependent switch mechanism, which effects the change in its function from molecular chaperone to protease. This mechanism is also related to substrate recognition and the fine control of its function. Structural and biochemical analyses of the three HtrA proteins, DegP, DegQ, and DegS, have provided us with clues as to the functional regulation of HtrA proteins, as well as their roles in protein quality control at atomic scales. The objective of this brief review is to discuss some of the recent studies which have been conducted regarding the structure and function of these HtrA proteins, and to compare their roles in the context of protein quality control.

Keywords

References

  1. Ades, S. E., Connolly, L. E., Alba, B. M. and Gross, C. A. (1999) The Escherichia coli $\sigma$(E)-dependent extracytoplasmic stress response is controlled by the regulated proteolysis of an anti-s factor. Genes Dev. 13, 2449-2461 https://doi.org/10.1101/gad.13.18.2449
  2. Alba, B. M. and Gross, C. A. (2004) Regulation of the Escherichia coli sE-dependent envelope stress response. Mol. Microbiol. 52, 613-619 https://doi.org/10.1111/j.1365-2958.2003.03982.x
  3. Alba, B. M., Leeds, J. A., Onufryk, C., Lu, C. Z. and Gross, C. A. (2002) DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response. Genes Dev. 16, 2156-2168 https://doi.org/10.1101/gad.1008902
  4. Alba, B. M., Zhong, H. J., Pelayo, J. C. and Gross, C. A. (2001) degS (hhoB) is an essential Escherichia coli gene whose indispensable function is to provide $\sigma$(E) activity. Mol. Microbiol. 40, 1323-1333 https://doi.org/10.1046/j.1365-2958.2001.02475.x
  5. Bakker, D., Vader, C. E., Roosendaal, B., Mooi, F. R., Oudega, B. and de Graaf, F. K. (1991) Structure and function of periplasmic chaperone-like proteins involved in the biosynthesis of K88 and K99 fimbriae in enterotoxigenic Escherichia coli. Mol. Microbiol. 5, 875-886 https://doi.org/10.1111/j.1365-2958.1991.tb00761.x
  6. Bass, S., Gu, Q. and Christin A. (1996) Multicopy suppressors of prc mutant Escherichia coli two HtrA (DegP) protease homologus (HhoAB), DksA, and a truncated R1pA. J. Bacteriol. 178, 1154-1161
  7. Baumler, A. J., Kusters, J. G., Stojiljkovic, I. and Heffron, F (1994) Salmonella typhimurium loci involved in survival within macrophages. Infect. Immun. 62, 1623-1630
  8. Cavard, C., Lazdunski, C. and Howard, S. P. (1989) The acylated precursor form of the colicin A lysis protein is a natural substrate of the DegP protease. J. Bacteriol. 171, 6316-6322
  9. Doyle, D. A., Lee, A., Lewis, J., Kim, E., Sheng, M. and Mackinno, R. (1996) Crystal structures of a complexed and peptide-free membrane protein-binding domain: Molecular basis of peptide recognition by PDZ. Cell 85, 1067-1076 https://doi.org/10.1016/S0092-8674(00)81307-0
  10. Elzer, P. H., Phillips, R. W., Robertson, G. T. and Roop II, R. M. (1996) The HtrA stress response protease contributes to resistance of Brucella abortus to killing by murine phagocytes. Infect. Immun. 64, 4838-4841
  11. Farn, J. and Roberts, M. (2004) Effect of inactivation of the HtrAlike serine protease DegQ on the virulence of Salmonella enterica serovar Typhimurium in mice. Infect Immun. 72, 7357- 7359 https://doi.org/10.1128/IAI.72.12.7357-7359.2004
  12. Gottesman, S. (2003) Proteolysis in bacterial regulatory circuits. Annu. Rev. Cell Dev. Biol. 19, 565-587 https://doi.org/10.1146/annurev.cellbio.19.110701.153228
  13. Gottesman, S., Wickner, S. and Maurizi, M. R. (1997) Protein quality control : triage by chaperone and proteases. Genes Dev. 11, 815-823 https://doi.org/10.1101/gad.11.7.815
  14. Harris, B. Z. and Lim, W. A. (2001) Mechanism and role of PDZ domains in signaling complex assembly. J. Cell Sci. 114, 3219- 3231
  15. Jones, C. H., Bolken, T. C., Jones, K. F., Zeller, G. O. and Hruby, D. E. (2001) Conserved DegP protease in gram-positive bacteria is essential for thermal and oxidative torlerance and full virulence in Streptococcus pyogenes. Infect. Immun. 69, 5538-5545 https://doi.org/10.1128/IAI.69.9.5538-5545.2001
  16. Jones, C. H., Dexter, P., Evans, A. K., Liu, C., Hultgren, S. J. and Hruby, D. E. (2002) Escherichia coli DegP protease cleaves between paired hydrophobic residues in a natural substrate: the PapA pilin. J. Bacteriol. 184, 5762-5771 https://doi.org/10.1128/JB.184.20.5762-5771.2002
  17. Kanehara, K., Ito, K. and Akiyama, Y. (2002) YaeL (EcfE) activates the sigma(E) pathway of stress response through a site-2 cleavage of anti-sigma(E), RseA. Genes Dev. 16, 2147- 2155 https://doi.org/10.1101/gad.1002302
  18. Kim, D. Y., Kim, D. R., Ha, S. C., Lokanath, N. K., Lee, C. J., Hwang, H. Y. and Kim, K. K. (2003) Crystal structure of the protease domain of a heat shock protein HtrA from Thermotoga maritime. J. Biol. Chem. 278, 6543-6551 https://doi.org/10.1074/jbc.M208148200
  19. Kim, D. Y. and Kim, K. K. (2002) Crystallization and preliminary X-ray studies of the protease domain of the heat-shock protein HtrA from Thermotoga maritima. Acta Crystallogr D Biol Crystallogr. 58, 170-172 https://doi.org/10.1107/S0907444901018248
  20. Kim, K. I., Park, S. C., Kang, S. H., Cheong, G. W. and Chung, C. H. (1999) Selective degradation of unfolded proteins by the self-compartmentalizing HtrA protease, a periplasmic heat shock protein in Escherichia coli. J. Mol. Biol. 294, 1363- 1374 https://doi.org/10.1006/jmbi.1999.3320
  21. Kolmar, H., Waller, P. R. and Sauer, R. T. (1996) The DegP and DegQ periplasmic endoproteases of Escherichia coli: specificity for cleavage sites and substrate conformation. J. Bacteriol. 178, 5925-5929
  22. Kraulis, P. J. (1991) Molscript. J. Appl. Crystallogr. 24, 946-950 https://doi.org/10.1107/S0021889891004399
  23. Krojer, T., Garrido-Franco, M., Huber, R., Ehrmann, M. and Clausen, T. (2002) Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine. Nature 416, 455-459 https://doi.org/10.1038/416455a
  24. Li, S. R., Dorrell, N., Everest, P. H., Dougan, G. and Wren, B. W. (1996) Construction and characterization of a Yersinia enterocolitica O:8 high-temperature requirement (htrA) isogenic mutant. Infect. Immun. 64, 2088-2094
  25. Li, W., Srinivasula, S. M., Chai, J., Li, P., Wu, J. -W., Zhang, Z., Alnemri, E. S. and Shi, Y. (2002) Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/ Omi. Nat. Struct. Biol. 9, 436-441 https://doi.org/10.1038/nsb795
  26. Lipinska, B., Sharma, S. and Georgopoulos, C. (1988) Sequence analysis and regulation of the htrA gene of Escherichia coli: a sigma 32-independent mechanism of heat-inducible transcription. Nucleic Acids Res. 16, 10053-10067 https://doi.org/10.1093/nar/16.21.10053
  27. Lipinska, B., Zylicz, M. and Georgopoulos, C. (1990) The HtrA (DegP) protein, essential for Escherichia coli survival at high temperatures, is an endopeptidase, J. Bacteriol. 172, 1791- 1797
  28. Pallen, M. J. and Ponting, C. P. (1997) PDZ domains in bacterial proteins. Mol. Microbiol. 26, 411-413 https://doi.org/10.1046/j.1365-2958.1997.5591911.x
  29. Pallen, M. J. and Wren, B. W. (1997) The HtrA family of serine proteases. Mol. Microbiol. 26, 209-221 https://doi.org/10.1046/j.1365-2958.1997.5601928.x
  30. Ponting, C. P. (1997) Evidence for PDZ domains in bacteria, yeast, and plants. Protein sci. 6, 464-468 https://doi.org/10.1002/pro.5560060225
  31. Poquet, I., Saint, V., Seznec, E., Simoes, N., Bolotin, A. and Gruss, A. (2000) HtrA is the unique surface housekeeping protease in Lactococcus lactis and is required for natural protein processing. Mol. Microbiol. 35, 1042-1051 https://doi.org/10.1046/j.1365-2958.2000.01757.x
  32. Raivio, T., and Silhavy, T. (2001) Periplasmic stress and ECF sigma factors. Annu. Rev. Microbiol. 55, 591-624 https://doi.org/10.1146/annurev.micro.55.1.591
  33. Skorko-Glonek, J., Krzewski, K., Lipinska, B., Bertoil, E. and Tanfani, F. (1995) comparison of the structure of wild-type HtrA heat shock protease and mutant HtrA proteins. A Fourier transform infrared spectroscopic study. J. Biol. Chem. 270, 11140-11146 https://doi.org/10.1074/jbc.270.19.11140
  34. Songyang, Z., Fanning, A. S., Fu, C., Xu, J., Marfatia, S. M., Chishti, A. H., Crompton, A., Chan, A. C., Anderson, J. M. and Cantley, L. C. (1997) Recognition of unique carboxylterminal motifs by distinct PDZ domains. Science 275, 73-77 https://doi.org/10.1126/science.275.5296.73
  35. Spiers, A., Lamb, H. K., Cocklin, S., Wheeler, K. A., Budworth, J., Dodds, A. L., Pallen, M. J., Maskell, D. J., Charles, I. G. and Hawkins, A. R. (2002) PDZ domains facilitate binding of high temperature requirement protease A (HtrA) and tailspecific protease (Tsp) to heterologous substrates through recognition of the small stable RNA A (ssrA)-encoded peptide. J. Biol. Chem. 277, 39443-39449 https://doi.org/10.1074/jbc.M202790200
  36. Spiess, C., Beil, A. and Ehrmann, M. (1999) A temperaturedependent switch from chaperone to protease in a widely conserved heat shock protein. Cell 97, 229-347
  37. Strauch, K. L. and Beckwith, J. (1988) An Escherichia coli mutation preventing degradation of abnormal periplasmic proteins. Proc. Natl. Acad. Sci. USA 85, 1576-1580 https://doi.org/10.1073/pnas.85.5.1576
  38. Swamy, K. H., Chung, C. H. and Goldberg, A. L. (1983) Isolation and characterization of protease do from Escherichia coli, a large serine protease containing multiple subunits. Arch. Biochem. Biophys. 224, 543-554 https://doi.org/10.1016/0003-9861(83)90242-4
  39. Thompson, J. D., Higgins, D. G. and Gibson, T. J. (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673-4680 https://doi.org/10.1093/nar/22.22.4673
  40. Waller, P. R. and Sauer, R. T. (1996) Characterization of degQ and degS, Escherichia coli genes encoding homologs of the DegP Protease. J. Bacteriol. 178, 1146-1153
  41. Walsh, N. P., Alba, B. M., Bose, B., Gross, C. A. and Sauer, R. T. (2003) OMP peptide signals initiate the envelope-stress response by activating DegS protease via relief of inhibition mediated by its PDZ domain. Cell 113, 61-71 https://doi.org/10.1016/S0092-8674(03)00203-4
  42. Wickner, S., Maurizi, M. R. and Gottesman, S. (1999) Posttranslational quality control: folding, refolding, and degrading proteins. Science 286, 1888-1893 https://doi.org/10.1126/science.286.5446.1888
  43. Wilken, C., Kitzing, K., Kurzbauer, R., Ehrmann, M. and Clausen, T. (2004) Crystal structure of the DegS stress sensor: How a PDZ domain recognizes misfolded protein and activates a protease. Cell 117, 483-494 https://doi.org/10.1016/S0092-8674(04)00454-4
  44. Wonderling, L. D., Wilkinson, B. J. and Bayles, D. O. (2004) The htrA(degP) gene of Listeria monocytogenes 10403S is essential for optimal growth under stress conditions. Appl. Environ. Microbiol. 70, 1935-1943 https://doi.org/10.1128/AEM.70.4.1935-1943.2004
  45. Wootton, J. C. and Drummond, M. H. (1989) The Q-linker - a class of interdomain sequences found in bacterial multidomain regulatory proteins. Protein Eng. 2, 535-543 https://doi.org/10.1093/protein/2.7.535
  46. Yorgey, P., Rahme, L. G., Tan, M. W. and Ausubel, F. M. (2001) The roles of mucD and alginatae in the virulence of Pseudomonas aeruginosa in plants, nematodes and mice. Mol. Microbiol. 41, 1063-1076 https://doi.org/10.1046/j.1365-2958.2001.02580.x

Cited by

  1. Botrytis cinerea BcNma is involved in apoptotic cell death but not in stress adaptation vol.48, pp.6, 2011, https://doi.org/10.1016/j.fgb.2011.01.007
  2. Campylobacter jejuniserine protease HtrA plays an important role in heat tolerance, oxygen resistance, host cell adhesion, invasion, and transmigration vol.5, pp.1, 2015, https://doi.org/10.1556/EuJMI-D-15-00003
  3. Periplasmic Proteins of the ExtremophileAcidithiobacillus ferrooxidans vol.6, pp.12, 2007, https://doi.org/10.1074/mcp.M700042-MCP200
  4. Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ vol.19, pp.2, 2012, https://doi.org/10.1038/nsmb.2210
  5. Using the SUBcellular database for Arabidopsis proteins to localize the Deg protease family vol.5, 2014, https://doi.org/10.3389/fpls.2014.00396
  6. Activation of HtrA2, a Mitochondrial Serine Protease Mediates Apoptosis: Current Knowledge on HtrA2 Mediated Myocardial Ischemia/Reperfusion Injury vol.26, pp.3, 2008, https://doi.org/10.1111/j.1755-5922.2008.00052.x
  7. The Mechanism of Temperature-Induced Bacterial HtrA Activation vol.377, pp.2, 2008, https://doi.org/10.1016/j.jmb.2007.12.078
  8. A gel-free quantitative proteomics approach to investigate temperature adaptation of the food-borne pathogen Cronobacter turicensis 3032 vol.10, pp.18, 2010, https://doi.org/10.1002/pmic.200900460
  9. Susceptibility of germ-free pigs to challenge with protease mutants of Salmonella enterica serovar Typhimurium vol.212, pp.7, 2007, https://doi.org/10.1016/j.imbio.2007.05.001
  10. Relapsing fever spirochaetes produce a serine protease that provides resistance to oxidative stress and killing by neutrophils vol.60, pp.3, 2006, https://doi.org/10.1111/j.1365-2958.2006.05122.x
  11. Global gene expression mediated by Thermus thermophilus SdrP, a CRP/FNR family transcriptional regulator vol.70, pp.1, 2008, https://doi.org/10.1111/j.1365-2958.2008.06388.x
  12. Molecular engineering of secretory machinery components for high-level secretion of proteins in Bacillus species vol.41, pp.11, 2014, https://doi.org/10.1007/s10295-014-1506-4
  13. High-energy water sites determine peptide binding affinity and specificity of PDZ domains vol.18, pp.8, 2009, https://doi.org/10.1002/pro.177
  14. Rapid characterization of the binding property of HtrA2/Omi PDZ domain by validation screening of PDZ ligand library vol.50, pp.3, 2007, https://doi.org/10.1007/s11427-007-0037-x
  15. Lyme disease spirochaetes possess an aggrecan-binding protease with aggrecanase activity 2013, https://doi.org/10.1111/mmi.12276
  16. The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies vol.108, pp.26, 2011, https://doi.org/10.1073/pnas.1101084108
  17. Virulence factors of theMycobacterium tuberculosiscomplex vol.4, pp.1, 2013, https://doi.org/10.4161/viru.22329
  18. Examination of post-transcriptional regulations in prokaryotes by integrative biology vol.332, pp.11, 2009, https://doi.org/10.1016/j.crvi.2009.09.005
  19. Prospective onMycobacterium tuberculosisProteomics vol.11, pp.1, 2012, https://doi.org/10.1021/pr2008658
  20. Production, secretion and purification of a correctly folded staphylococcal antigen in Lactococcus lactis vol.14, pp.1, 2015, https://doi.org/10.1186/s12934-015-0271-z
  21. Insights into the Cyanobacterial Deg/HtrA Proteases vol.7, 2016, https://doi.org/10.3389/fpls.2016.00694
  22. Bacterial proteolytic complexes as therapeutic targets vol.11, pp.10, 2012, https://doi.org/10.1038/nrd3846
  23. Distinct Biological Potential of Streptococcus gordonii and Streptococcus sanguinis Revealed by Comparative Genome Analysis vol.7, pp.1, 2017, https://doi.org/10.1038/s41598-017-02399-4
  24. The role of serine protease HtrA in acute ulcerative enterocolitis and extra-intestinal immune responses during Campylobacter jejuni infection of gnotobiotic IL-10 deficient mice vol.4, 2014, https://doi.org/10.3389/fcimb.2014.00077
  25. Allosteric Activation of DegS, a Stress Sensor PDZ Protease vol.131, pp.3, 2007, https://doi.org/10.1016/j.cell.2007.08.044
  26. The thylakoid protease Deg1 is involved in photosystem-II assembly in Arabidopsis thaliana vol.62, pp.2, 2010, https://doi.org/10.1111/j.1365-313X.2010.04140.x
  27. Solution structure of Q388A3 PDZ domain from Trypanosoma brucei vol.194, pp.2, 2016, https://doi.org/10.1016/j.jsb.2016.02.018
  28. Analysis of Edwardsiella tarda DegP, a serine protease and a protective immunogen vol.28, pp.4, 2010, https://doi.org/10.1016/j.fsi.2010.01.004
  29. A secretory multifunctional serine protease, DegP ofPlasmodium falciparum, plays an important role in thermo-oxidative stress, parasite growth and development vol.281, pp.6, 2014, https://doi.org/10.1111/febs.12732
  30. Signaling mechanisms for activation of extracytoplasmic function (ECF) sigma factors vol.1778, pp.9, 2008, https://doi.org/10.1016/j.bbamem.2007.06.005
  31. Comparative analysis of gene expression profiles between the normal human cartilage and the one with endemic osteoarthritis vol.17, pp.1, 2009, https://doi.org/10.1016/j.joca.2008.05.008
  32. The HtrA/DegP family protease MamE is a bifunctional protein with roles in magnetosome protein localization and magnetite biomineralization vol.80, pp.4, 2011, https://doi.org/10.1111/j.1365-2958.2011.07631.x
  33. Control ofPseudomonas aeruginosaAlgW protease cleavage of MucA by peptide signals and MucB vol.72, pp.2, 2009, https://doi.org/10.1111/j.1365-2958.2009.06654.x
  34. Deg proteases and their role in protein quality control and processing in different subcellular compartments of the plant cell vol.145, pp.1, 2012, https://doi.org/10.1111/j.1399-3054.2011.01533.x
  35. Chaperone–protease networks in mitochondrial protein homeostasis vol.1833, pp.2, 2013, https://doi.org/10.1016/j.bbamcr.2012.06.005
  36. Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin vol.4, pp.1, 2012, https://doi.org/10.1186/1757-4749-4-3
  37. The mitochondrial serine protease HtrA2/Omi: an overview vol.15, pp.3, 2008, https://doi.org/10.1038/sj.cdd.4402291
  38. OMP Peptides Activate the DegS Stress-Sensor Protease by a Relief of Inhibition Mechanism vol.17, pp.10, 2009, https://doi.org/10.1016/j.str.2009.07.017
  39. OMP Peptides Modulate the Activity of DegS Protease by Differential Binding to Active and Inactive Conformations vol.33, pp.1, 2009, https://doi.org/10.1016/j.molcel.2008.12.017
  40. Analysis of the DNA region mediating increased thermotolerance at 58°C in Cronobacter sp. and other enterobacterial strains vol.100, pp.2, 2011, https://doi.org/10.1007/s10482-011-9585-y
  41. Protein Degradation within Mitochondria: Versatile Activities of AAA Proteases and Other Peptidases vol.42, pp.3, 2007, https://doi.org/10.1080/10409230701380452
  42. The structural basis of mode of activation and functional diversity: A case study with HtrA family of serine proteases vol.516, pp.2, 2011, https://doi.org/10.1016/j.abb.2011.10.007
  43. Autotransporter secretion: varying on a theme vol.164, pp.6, 2013, https://doi.org/10.1016/j.resmic.2013.03.010
  44. Structural Insight into Serine Protease Rv3671c that Protects M. tuberculosis from Oxidative and Acidic Stress vol.18, pp.10, 2010, https://doi.org/10.1016/j.str.2010.06.017
  45. Structural and Functional Analysis of HtrA1 and Its Subdomains vol.20, pp.6, 2012, https://doi.org/10.1016/j.str.2012.03.021
  46. Extracellular secretion of protease HtrA fromCampylobacter jejuniis highly efficient and independent of its protease activity and flagellum vol.3, pp.3, 2013, https://doi.org/10.1556/EuJMI.3.2013.3.3
  47. Genetic determinants of heat resistance in Escherichia coli vol.6, 2015, https://doi.org/10.3389/fmicb.2015.00932
  48. Cell envelope stress response in Gram-positive bacteria vol.32, pp.1, 2008, https://doi.org/10.1111/j.1574-6976.2007.00091.x
  49. Mitochondrial protein quality control in health and disease vol.171, pp.8, 2014, https://doi.org/10.1111/bph.12430
  50. Role of group AStreptococcus HtrA in the maturation of SpeB protease vol.7, pp.24, 2007, https://doi.org/10.1002/pmic.200700626
  51. Architecture and regulation of HtrA-family proteins involved in protein quality control and stress response vol.70, pp.5, 2013, https://doi.org/10.1007/s00018-012-1076-4
  52. Metabolite stress and tolerance in the production of biofuels and chemicals: Gene-expression-based systems analysis of butanol, butyrate, and acetate stresses in the anaerobeClostridium acetobutylicum 2010, https://doi.org/10.1002/bit.22628
  53. Unraveling tobacco BY-2 protein complexes with BN PAGE/LC–MS/MS and clustering methods vol.74, pp.8, 2011, https://doi.org/10.1016/j.jprot.2011.03.023
  54. Characterization of the Structure and Function of Escherichia coli DegQ as a Representative of the DegQ-like Proteases of Bacterial HtrA Family Proteins vol.19, pp.9, 2011, https://doi.org/10.1016/j.str.2011.06.013
  55. Escherichia coli exhibits a membrane-related response to a small arginine- and tryptophan-rich antimicrobial peptide vol.12, pp.14, 2012, https://doi.org/10.1002/pmic.201100636
  56. The HtrA-Like Protease CD3284 Modulates Virulence of Clostridium difficile vol.82, pp.10, 2014, https://doi.org/10.1128/IAI.02336-14
  57. Amino-Terminal Processing of Helicobacter pylori Serine Protease HtrA: Role in Oligomerization and Activity Regulation vol.9, pp.1664-302X, 2018, https://doi.org/10.3389/fmicb.2018.00642
  58. PDZ domains and their binding partners: structure, specificity, and modification vol.8, pp.1, 2010, https://doi.org/10.1186/1478-811X-8-8
  59. Distinct Contribution of the HtrA Protease and PDZ Domains to Its Function in Stress Resilience and Virulence of Bacillus anthracis vol.10, pp.1664-302X, 2019, https://doi.org/10.3389/fmicb.2019.00255