Structural and functional analysis of human HtrA3 protease and its subdomains

Glaza, Przemyslaw; Osipiuk, Jerzy; Wenta, Tomasz; Zurawa-Janicka, Dorota; Jarzab, Miroslaw; Lesner, Adam; Banecki, Bogdan; Skorko-Glonek, Joanna; Joachimiak, Andrzej; Lipinska, Barbara; van Raaij, Mark J.

doi:10.1371/journal.pone.0131142

Structural and functional analysis of human HtrA3 protease and its subdomains

Journal Article · Thu Jun 25 04:00:00 EDT 2015 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0131142· OSTI ID:1212403

Glaza, Przemyslaw ^[1]; Osipiuk, Jerzy ^[2]; Wenta, Tomasz ^[1]; Zurawa-Janicka, Dorota ^[1]; Jarzab, Miroslaw ^[1]; Lesner, Adam ^[1]; Banecki, Bogdan ^[3]; Skorko-Glonek, Joanna ^[1]; Joachimiak, Andrzej ^[2]; Lipinska, Barbara ^[1]; van Raaij, Mark J. ^[4]

Univ. of Gdansk (Poland). Dept. of Biochemistry.
Argonne National Lab., Argonne, IL (United States). Midwest Center for Structural Genomics and Structural Biology Center.
Univ. of Gdansk (Poland). Dept. of Molecular and Cellular Biology; Medical Univ. of Gdansk (Poland)
Centro Nacional de Biotecnologia - CSIC (Spain)

Human HtrA3 protease, which induces mitochondria-mediated apoptosis, can be a tumor suppressor and a potential therapeutic target in the treatment of cancer. However, there is little information about its structure and biochemical properties. HtrA3 is composed of an N-terminal domain not required for proteolytic activity, a central serine protease domain and a C-terminal PDZ domain. HtrA3S, its short natural isoform, lacks the PDZ domain which is substituted by a stretch of 7 C-terminal amino acid residues, unique for this isoform. This paper presents the crystal structure of the HtrA3 protease domain together with the PDZ domain (ΔN-HtrA3), showing that the protein forms a trimer whose protease domains are similar to those of human HtrA1 and HtrA2. The ΔN-HtrA3 PDZ domains are placed in a position intermediate between that in the flat saucer-like HtrA1 SAXS structure and the compact pyramidal HtrA2 X-ray structure. The PDZ domain interacts closely with the LB loop of the protease domain in a way not found in other human HtrAs. ΔN-HtrA3 with the PDZ removed (ΔN-HtrA3-ΔPDZ) and an N-terminally truncated HtrA3S (ΔN-HtrA3S) were fully active at a wide range of temperatures and their substrate affinity was not impaired. This indicates that the PDZ domain is dispensable for HtrA3 activity. As determined by size exclusion chromatography, ΔN-HtrA3 formed stable trimers while both ΔN-HtrA3-ΔPDZ and ΔN-HtrA3S were monomeric. This suggests that the presence of the PDZ domain, unlike in HtrA1 and HtrA2, influences HtrA3 trimer formation. The unique C-terminal sequence of ΔN-HtrA3S appeared to have little effect on activity and oligomerization. Additionally, we examined the cleavage specificity of ΔN-HtrA3. Results reported in this paper provide new insights into the structure and function of ΔN-HtrA3, which seems to have a unique combination of features among human HtrA proteases.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23); National Institute of Health; National Science Center (Poland)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1212403

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 6 Vol. 10; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (73)

Architecture and regulation of HtrA-family proteins involved in protein quality control and stress response Hansen, Guido; Hilgenfeld, Rolf Cellular and Molecular Life Sciences, Vol. 70, Issue 5 https://doi.org/10.1007/s00018-012-1076-4	journal	July 2012
Allosteric Activation of a Bacterial Stress Sensor Yan, Nieng; Shi, Yigong Cell, Vol. 131, Issue 3 https://doi.org/10.1016/j.cell.2007.10.021	journal	November 2007
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
High-temperature requirement factor A3 (Htra3): A novel serine protease and its potential role in ovarian function and ovarian cancers Bowden, Marissa A.; Drummond, Ann E.; Fuller, Peter J. Molecular and Cellular Endocrinology, Vol. 327, Issue 1-2 https://doi.org/10.1016/j.mce.2010.06.001	journal	October 2010
Inhibition of HTRA3 stimulates trophoblast invasion during human placental development Singh, H.; Makino, S. -i.; Endo, Y. Placenta, Vol. 31, Issue 12 https://doi.org/10.1016/j.placenta.2010.10.003	journal	December 2010
A Stress Sensor for the Bacterial Periplasm Young, Jason C.; Hartl, F. Ulrich Cell, Vol. 113, Issue 1 https://doi.org/10.1016/s0092-8674(03)00192-2	journal	April 2003
A PDZ Switch for a Cellular Stress Response Schlieker, Christian; Mogk, Axel; Bukau, Bernd Cell, Vol. 117, Issue 4 https://doi.org/10.1016/s0092-8674(04)00453-2	journal	May 2004
The N-terminal region of HtrA heat shock protease from Escherichia coli is essential for stabilization of HtrA primary structure and maintaining of its oligomeric structure Skórko-Glonek, Joanna; Żurawa, Dorota; Tanfani, Fabio Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1649, Issue 2 https://doi.org/10.1016/s1570-9639(03)00170-5	journal	July 2003
Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine Krojer, Tobias; Garrido-Franco, Marta; Huber, Robert Nature, Vol. 416, Issue 6879 https://doi.org/10.1038/416455a	journal	March 2002
The homotrimeric structure of HtrA2 is indispensable for executing its serine protease activity Nam, Min-Kyung; Seong, Young-Mo; Park, Hyo-Jin Experimental & Molecular Medicine, Vol. 38, Issue 1 https://doi.org/10.1038/emm.2006.5	journal	February 2006
Structural basis for the regulated protease and chaperone function of DegP Krojer, Tobias; Sawa, Justyna; Schäfer, Eva Nature, Vol. 453, Issue 7197 https://doi.org/10.1038/nature07004	journal	May 2008
HTRA proteases: regulated proteolysis in protein quality control Clausen, Tim; Kaiser, Markus; Huber, Robert Nature Reviews Molecular Cell Biology, Vol. 12, Issue 3 https://doi.org/10.1038/nrm3065	journal	February 2011
HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues Krojer, Tobias; Sawa, Justyna; Huber, Robert Nature Structural & Molecular Biology, Vol. 17, Issue 7 https://doi.org/10.1038/nsmb.1840	journal	June 2010
Substrate-induced remodeling of the active site regulates human HTRA1 activity Truebestein, Linda; Tennstaedt, Annette; Mönig, Timon Nature Structural & Molecular Biology, Vol. 18, Issue 3 https://doi.org/10.1038/nsmb.2013	journal	February 2011
PDZ domains determine the native oligomeric structure of the DegP (HtrA) protease Sassoon, Nathalie; Arie, Jean-Philippe; Betton, Jean-Michel Molecular Microbiology, Vol. 33, Issue 3 https://doi.org/10.1046/j.1365-2958.1999.01505.x	journal	August 1999
Activation of DegP chaperone-protease via formation of large cage-like oligomers upon binding to substrate proteins Jiang, J.; Zhang, X.; Chen, Y. Proceedings of the National Academy of Sciences, Vol. 105, Issue 33 https://doi.org/10.1073/pnas.0805464105	journal	August 2008
The Legionella HtrA homologue DegQ is a self-compartmentizing protease that forms large 12-meric assemblies Wrase, R.; Scott, H.; Hilgenfeld, R. Proceedings of the National Academy of Sciences, Vol. 108, Issue 26 https://doi.org/10.1073/pnas.1101084108	journal	June 2011
Cage assembly of DegP protease is not required for substrate-dependent regulation of proteolytic activity or high-temperature cell survival Kim, S.; Sauer, R. T. Proceedings of the National Academy of Sciences, Vol. 109, Issue 19 https://doi.org/10.1073/pnas.1204791109	journal	April 2012
Comparison of the structure of wild-type HtrA heat shock protease and mutant HtrA proteins. A Fourier transform infrared spectroscopic study. Skórko-Glonek, Joanna; Krzewski, Konrad; Lipinska, Barbara Journal of Biological Chemistry, Vol. 270, Issue 52 https://doi.org/10.1074/jbc.270.52.31413	journal	December 1995
High Temperature Requirement A3 (HtrA3) Promotes Etoposide- and Cisplatin-induced Cytotoxicity in Lung Cancer Cell Lines Beleford, Daniah; Rattan, Ramandeep; Chien, Jeremy Journal of Biological Chemistry, Vol. 285, Issue 16 https://doi.org/10.1074/jbc.m109.097790	journal	February 2010
A novel serine protease of the mammalian HtrA family is up-regulated in mouse uterus coinciding with placentation Nie, G. -Y. Molecular Human Reproduction, Vol. 9, Issue 5 https://doi.org/10.1093/molehr/gag036	journal	May 2003
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes Minor, Wladek; Cymborowski, Marcin; Otwinowski, Zbyszek Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8 https://doi.org/10.1107/s0907444906019949	journal	July 2006
Pi sampling: a methodical and flexible approach to initial macromolecular crystallization screening Gorrec, Fabrice; Palmer, Colin M.; Lebon, Guillaume Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 5 https://doi.org/10.1107/s0907444911008754	journal	April 2011
The CCP4 suite programs for protein crystallography No authors listed Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763 https://doi.org/10.1107/s0907444994003112	journal	September 1994
The Structural Biology Center 19ID undulator beamline: facility specifications and protein crystallographic results Rosenbaum, Gerd; Alkire, Randy W.; Evans, Gwyndaf Journal of Synchrotron Radiation, Vol. 13, Issue 1 https://doi.org/10.1107/s0909049505036721	journal	December 2005
Structural and functional analysis of the PDZ domains of human HtrA1 and HtrA3 Runyon, Steven T.; Zhang, Yingnan; Appleton, Brent A. Protein Science, Vol. 16, Issue 11 https://doi.org/10.1110/ps.073049407	journal	November 2007
Developmentally regulated expression of mouse HtrA3 and its role as an inhibitor of TGF-beta signaling Tocharus, Jiraporn; Tsuchiya, Akiho; Kajikawa, Miwa Development, Growth and Differentiation, Vol. 46, Issue 3 https://doi.org/10.1111/j.1440-169x.2004.00743.x	journal	June 2004
Role of the PDZ Domains in Escherichia coli DegP Protein Iwanczyk, Jack; Damjanovic, Daniela; Kooistra, Joel Journal of Bacteriology, Vol. 189, Issue 8 https://doi.org/10.1128/jb.01788-06	journal	February 2007
The HtrA (DegP) protein, essential for Escherichia coli survival at high temperatures, is an endopeptidase. Lipinska, B.; Zylicz, M.; Georgopoulos, C. Journal of Bacteriology, Vol. 172, Issue 4 https://doi.org/10.1128/jb.172.4.1791-1797.1990	journal	January 1990
Methylation Induced Gene Silencing of HtrA3 in Smoking-Related Lung Cancer Beleford, D.; Liu, Z.; Rattan, R. Clinical Cancer Research, Vol. 16, Issue 2 https://doi.org/10.1158/1078-0432.ccr-09-1677	journal	January 2010
Application of the wheat-germ cell-free translation system to produce high temperature requirement A3 (HtrA3) proteases Singh, Harmeet; Makino, Shin-ichi; Endo, Yaeta BioTechniques, Vol. 52, Issue 1 https://doi.org/10.2144/000113798	journal	January 2012
HtrA Protease Family as Therapeutic Targets Skorko-Glonek, Joanna; Zurawa-Janicka, Dorota; Koper, Tomasz Current Pharmaceutical Design, Vol. 19, Issue 6 https://doi.org/10.2174/1381612811319060003	journal	December 2012
Expression of human HtrA1, HtrA2, HtrA3 and TGF-β1 genes in primary endometrial cancer No authors listed Oncology Reports, Vol. 21, Issue 6 https://doi.org/10.3892/or_00000385	journal	May 2009
Distinct expression and localization of serine protease HtrA1 in human endometrium and first-trimester placenta Nie, Guiying; Hale, Kathryn; Li, Ying Developmental Dynamics, Vol. 235, Issue 12 https://doi.org/10.1002/dvdy.20999	journal	December 2006
Structural basis of substrate specificity in the serine proteases Perona, John J.; Craik, Charles S. Protein Science, Vol. 4, Issue 3 https://doi.org/10.1002/pro.5560040301	journal	March 1995
Temperature-induced changes of HtrA2(Omi) protease activity and structure Zurawa-Janicka, Dorota; Jarzab, Miroslaw; Polit, Agnieszka Cell Stress and Chaperones, Vol. 18, Issue 1 https://doi.org/10.1007/s12192-012-0355-1	journal	August 2012
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding Bradford, Marion M. Analytical Biochemistry, Vol. 72, Issue 1-2 https://doi.org/10.1016/0003-2697(76)90527-3	journal	May 1976
Protein degradation in E. coli: The ion mutation and bacteriophage lambda N and cll protein stability Gottesman, S. Cell, Vol. 24, Issue 1 https://doi.org/10.1016/0092-8674(81)90518-3	journal	April 1981
OMP Peptide Signals Initiate the Envelope-Stress Response by Activating DegS Protease via Relief of Inhibition Mediated by Its PDZ Domain Walsh, Nathan P.; Alba, Benjamin M.; Bose, Baundauna Cell, Vol. 113, Issue 1 https://doi.org/10.1016/S0092-8674(03)00203-4	journal	April 2003
Crystal Structure of the DegS Stress Sensor Wilken, Corinna; Kitzing, Karina; Kurzbauer, Robert Cell, Vol. 117, Issue 4 https://doi.org/10.1016/S0092-8674(04)00454-4	journal	May 2004
The N-terminal region of HtrA heat shock protease from Escherichia coli is essential for stabilization of HtrA primary structure and maintaining of its oligomeric structure Skórko-Glonek, Joanna; Żurawa, Dorota; Tanfani, Fabio Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1649, Issue 2 https://doi.org/10.1016/S1570-9639(03)00170-5	journal	July 2003
Allosteric Activation of DegS, a Stress Sensor PDZ Protease Sohn, Jungsan; Grant, Robert A.; Sauer, Robert T. Cell, Vol. 131, Issue 3 https://doi.org/10.1016/j.cell.2007.08.044	journal	November 2007
Covalent Linkage of Distinct Substrate Degrons Controls Assembly and Disassembly of DegP Proteolytic Cages Kim, Seokhee; Grant, Robert A.; Sauer, Robert T. Cell, Vol. 145, Issue 1 https://doi.org/10.1016/j.cell.2011.02.024	journal	April 2011
Changes in mRNA and protein levels of human HtrA1, HtrA2 and HtrA3 in ovarian cancer Narkiewicz, Joanna; Klasa-Mazurkiewicz, Dagmara; Zurawa-Janicka, Dorota Clinical Biochemistry, Vol. 41, Issue 7-8 https://doi.org/10.1016/j.clinbiochem.2008.01.004	journal	May 2008
Prediction of Preeclampsia – A Workshop Report Than, N. G.; Romero, R.; Hillermann, R. Placenta, Vol. 29 https://doi.org/10.1016/j.placenta.2007.10.008	journal	March 2008
Structural and Functional Analysis of HtrA1 and Its Subdomains Eigenbrot, Charles; Ultsch, Mark; Lipari, Michael T. Structure, Vol. 20, Issue 6 https://doi.org/10.1016/j.str.2012.03.021	journal	June 2012
Serine proteases HTRA1 and HTRA3 are down-regulated with increasing grades of human endometrial cancer Bowden, Marissa A.; Di Nezza-Cossens, Lisa A.; Jobling, Tom Gynecologic Oncology, Vol. 103, Issue 1 https://doi.org/10.1016/j.ygyno.2006.03.006	journal	October 2006
Structure and Function of the Virulence-Associated High-Temperature Requirement A of Mycobacterium tuberculosis ^† ^‡ MohamedMohaideen, Nilofar N.; Palaninathan, Satheesh K.; Morin, Paul M. Biochemistry, Vol. 47, Issue 23 https://doi.org/10.1021/bi701929m	journal	June 2008
Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi Li, Wenyu; Srinivasula, Srinivasa M.; Chai, Jijie Nature Structural Biology, Vol. 9, Issue 6 https://doi.org/10.1038/nsb795	journal	April 2002
Identification and cloning of two isoforms of human high-temperature requirement factor A3 (HtrA3), characterization of its genomic structure and comparison of its tissue distribution with HtrA1 and HtrA2 Nie, Gui-Ying; Hampton, Anne; Li, Ying Biochemical Journal, Vol. 371, Issue 1 https://doi.org/10.1042/bj20021569	journal	April 2003
Interplay of PDZ and protease domain of DegP ensures efficient elimination of misfolded proteins Krojer, T.; Pangerl, K.; Kurt, J. Proceedings of the National Academy of Sciences, Vol. 105, Issue 22 https://doi.org/10.1073/pnas.0803392105	journal	May 2008
High Temperature Requirement A3 (HtrA3) Promotes Etoposide- and Cisplatin-induced Cytotoxicity in Lung Cancer Cell Lines Beleford, Daniah; Rattan, Ramandeep; Chien, Jeremy Journal of Biological Chemistry, Vol. 285, Issue 16 https://doi.org/10.1074/jbc.M109.097790	journal	February 2010
Allostery Is an Intrinsic Property of the Protease Domain of DegS: IMPLICATIONS FOR ENZYME FUNCTION AND EVOLUTION Sohn, Jungsan; Grant, Robert A.; Sauer, Robert T. Journal of Biological Chemistry, Vol. 285, Issue 44 https://doi.org/10.1074/jbc.M110.135541	journal	August 2010
The LA Loop as an Important Regulatory Element of the HtrA (DegP) Protease from Escherichia coli: STRUCTURAL AND FUNCTIONAL STUDIES Figaj, Donata; Gieldon, Artur; Polit, Agnieszka Journal of Biological Chemistry, Vol. 289, Issue 22 https://doi.org/10.1074/jbc.M113.532895	journal	April 2014
Binding Specificity and Regulation of the Serine Protease and PDZ Domains of HtrA2/Omi Martins, L. Miguel; Turk, Benjamin E.; Cowling, Victoria Journal of Biological Chemistry, Vol. 278, Issue 49 https://doi.org/10.1074/jbc.M308659200	journal	September 2003
MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes Davis, I. W.; Murray, L. W.; Richardson, J. S. Nucleic Acids Research, Vol. 32, Issue Web Server https://doi.org/10.1093/nar/gkh398	journal	July 2004
Dali server: conservation mapping in 3D Holm, Liisa; Rosenstrï¿½m, Pï¿½ivi Nucleic Acids Research, Vol. 38, Issue suppl_2 https://doi.org/10.1093/nar/gkq366	journal	May 2010
Serine Peptidase HTRA3 Is Closely Associated with Human Placental Development and Is Elevated in Pregnancy Serum1 Nie, Guiying; Li, Ying; Hale, Kathryn Biology of Reproduction, Vol. 74, Issue 2 https://doi.org/10.1095/biolreprod.105.047324	journal	February 2006
CHAINSAW : a program for mutating pdb files used as templates in molecular replacement Stein, Norman Journal of Applied Crystallography, Vol. 41, Issue 3 https://doi.org/10.1107/S0021889808006985	journal	April 2008
PHENIX : building new software for automated crystallographic structure determination Adams, Paul D.; Grosse-Kunstleve, Ralf W.; Hung, Li-Wei Acta Crystallographica Section D Biological Crystallography, Vol. 58, Issue 11 https://doi.org/10.1107/S0907444902016657	journal	October 2002
Coot model-building tools for molecular graphics Emsley, Paul; Cowtan, Kevin Acta Crystallographica Section D Biological Crystallography, Vol. 60, Issue 12, p. 2126-2132 https://doi.org/10.1107/S0907444904019158	journal	November 2004
HKL -3000: the integration of data reduction and structure solution – from diffraction images to an initial model in minutes Minor, Wladek; Cymborowski, Marcin; Otwinowski, Zbyszek Acta Crystallographica Section D Biological Crystallography, Vol. 62, Issue 8 https://doi.org/10.1107/S0907444906019949	journal	July 2006
Molecular replacement with MOLREP Vagin, Alexei; Teplyakov, Alexei Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042589	journal	December 2009
Pi sampling: a methodical and flexible approach to initial macromolecular crystallization screening Gorrec, Fabrice; Palmer, Colin M.; Lebon, Guillaume Acta Crystallographica Section D Biological Crystallography, Vol. 67, Issue 5 https://doi.org/10.1107/S0907444911008754	journal	April 2011
The CCP4 suite programs for protein crystallography No authors listed Acta Crystallographica Section D Biological Crystallography, Vol. 50, Issue 5, p. 760-763 https://doi.org/10.1107/S0907444994003112	journal	September 1994
The Structural Biology Center 19ID undulator beamline: facility specifications and protein crystallographic results Rosenbaum, Gerd; Alkire, Randy W.; Evans, Gwyndaf Journal of Synchrotron Radiation, Vol. 13, Issue 1 https://doi.org/10.1107/S0909049505036721	journal	December 2005
Developmentally regulated expression of mouse HtrA3 and its role as an inhibitor of TGF-beta signaling Tocharus, Jiraporn; Tsuchiya, Akiho; Kajikawa, Miwa Development, Growth and Differentiation, Vol. 46, Issue 3 https://doi.org/10.1111/j.1440-169X.2004.00743.x	journal	June 2004
Role of the PDZ Domains in Escherichia coli DegP Protein Iwanczyk, Jack; Damjanovic, Daniela; Kooistra, Joel Journal of Bacteriology, Vol. 189, Issue 8 https://doi.org/10.1128/JB.01788-06	journal	February 2007
Methylation Induced Gene Silencing of HtrA3 in Smoking-Related Lung Cancer Beleford, D.; Liu, Z.; Rattan, R. Clinical Cancer Research, Vol. 16, Issue 2 https://doi.org/10.1158/1078-0432.CCR-09-1677	journal	January 2010
Placental HtrA3 Is Regulated by Oxygen Tension and Serum Levels Are Altered during Early Pregnancy in Women Destined to Develop Preeclampsia Li, Ying; Puryer, Michelle; Lin, Eliane The Journal of Clinical Endocrinology & Metabolism, Vol. 96, Issue 2 https://doi.org/10.1210/jc.2010-1405	journal	February 2011
HtrA3 as an Early Marker for Preeclampsia: Specific Monoclonal Antibodies and Sensitive High-Throughput Assays for Serum Screening Dynon, Kemperly; Heng, Sophea; Puryer, Michelle PLoS ONE, Vol. 7, Issue 9 https://doi.org/10.1371/journal.pone.0045956	journal	September 2012
HtrA Serine Proteases as Potential Therapeutic Targets in Cancer Chien, Jeremy; Campioni, Mara; Shridhar, Viji Current Cancer Drug Targets, Vol. 9, Issue 4 https://doi.org/10.2174/156800909788486704	journal	June 2009
HTRA3 is Reduced in Ovarian Cancers Regardless of Stage Zhao, M.; Ding, J. X.; Nie, G. Y. Cancer Investigation, Vol. 32, Issue 9 https://doi.org/10.3109/07357907.2014.958496	journal	September 2014

Cited By (9)

A distinct concerted mechanism of structural dynamism defines activity of human serine protease HtrA3 Acharya, Saujanya; Dutta, Shubhankar; Bose, Kakoli Biochemical Journal, Vol. 477, Issue 2 https://doi.org/10.1042/bcj20190706	journal	January 2020
A Cell Proliferation and Inflammatory Signature is Induced by Lawsonia intracellularis Infection in Swine Leite, Fernando L.; Abrahante, Juan E.; Vasquez, Erika mBio https://doi.org/10.1101/384230	journal	August 2018
Role of HTRA1 in bone formation and regeneration: In vitro and in vivo evaluation Filliat, Gladys; Mirsaidi, Ali; Tiaden, André N. PLOS ONE, Vol. 12, Issue 7 https://doi.org/10.1371/journal.pone.0181600	journal	July 2017
Integration of genomic, transcriptomic and functional profiles of aggressive osteosarcomas across multiple species Davis, Lara E.; Jeng, Sophia; Svalina, Matthew N. Oncotarget, Vol. 8, Issue 44 https://doi.org/10.18632/oncotarget.19532	journal	July 2017
High temperature requirement A3 (HTRA3) expression predicts postoperative recurrence and survival in patients with non-small-cell lung cancer Zhao, Jingya; Zhang, Jing; Zhang, Xin Oncotarget, Vol. 7, Issue 26 https://doi.org/10.18632/oncotarget.9173	journal	May 2016
Properties of the HtrA Protease From Bacterium Helicobacter pylori Whose Activity Is Indispensable for Growth Under Stress Conditions Zarzecka, Urszula; Modrak-Wójcik, Anna; Figaj, Donata Frontiers in Microbiology, Vol. 10 https://doi.org/10.3389/fmicb.2019.00961	journal	May 2019
HtrA4 Protease Promotes Chemotherapeutic-Dependent Cancer Cell Death No authors listed Cells, Vol. 8, Issue 10 https://doi.org/10.3390/cells8101112	journal	September 2019
Discerning the mechanism of action of HtrA4: a serine protease implicated in the cell death pathway Kummari, Raghupathi; Dutta, Shubhankar; Chaganti, Lalith K. Biochemical Journal, Vol. 476, Issue 10 https://doi.org/10.1042/bcj20190224	journal	May 2019
Distinct 3D Architecture and Dynamics of the Human HtrA2(Omi) Protease and Its Mutated Variants Gieldon, Artur; Zurawa-Janicka, Dorota; Jarzab, Miroslaw PLOS ONE, Vol. 11, Issue 8 https://doi.org/10.1371/journal.pone.0161526	journal	August 2016

Similar Records

Structure and Function of the Virulence-Associated High-Temperature Requirement A of Mycobacterium tuberculosis

Journal Article · Fri Jun 13 00:00:00 EDT 2008 · Biochemistry-US · OSTI ID:1006626

Structural And Functional Analysis of the Ligand Specificity of the HtrA2/OmI PDZ Domain

Journal Article · Thu Jun 04 00:00:00 EDT 2009 · Protein Sci. 16:1738,2007 · OSTI ID:953913

The structures of Arabidopsis Deg5 and Deg8 reveal new insights into HtrA proteases

Journal Article · Wed May 01 00:00:00 EDT 2013 · Acta Crystallographica. Section D: Biological Crystallography · OSTI ID:22347842

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
X-ray crystallography
crystal structure
oligomers
peptides
proteases
protein structure
serine proteases
size-exclusion chromatography

Structural and functional analysis of human HtrA3 protease and its subdomains

Citation Formats

References (73)

Cited By (9)

Similar Records

Related Subjects