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Substrate-induced remodeling of the active site regulates human HTRA1 activity.

Truebestein L, Tennstaedt A, Mönig T, Krojer T, Canellas F, Kaiser M, Clausen T, Ehrmann M
Nat Struct Mol Biol 18 386-8 (2011)
Related entries: 3nwu, 3nzi

Cited: 75 times
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Abstract

Crystal structures of active and inactive conformations of the human serine protease HTRA1 reveal that substrate binding to the active site is sufficient to stimulate proteolytic activity. HTRA1 attaches to liposomes, digests misfolded proteins into defined fragments and undergoes substrate-mediated oligomer conversion. In contrast to those of other serine proteases, the PDZ domain of HTRA1 is dispensable for activation or lipid attachment, indicative of different underlying mechanistic features.

Articles - 3num mentioned but not cited (6)

  1. Structural and Functional Analysis of Human HtrA3 Protease and Its Subdomains. Glaza P, Osipiuk J, Wenta T, Zurawa-Janicka D, Jarzab M, Lesner A, Banecki B, Skorko-Glonek J, Joachimiak A, Lipinska B. PLoS One 10 e0131142 (2015)
  2. HtrA1 activation is driven by an allosteric mechanism of inter-monomer communication. Cabrera AC, Melo E, Roth D, Topp A, Delobel F, Stucki C, Chen CY, Jakob P, Banfai B, Dunkley T, Schilling O, Huber S, Iacone R, Petrone P. Sci Rep 7 14804 (2017)
  3. The structures of Arabidopsis Deg5 and Deg8 reveal new insights into HtrA proteases. Sun W, Gao F, Fan H, Shan X, Sun R, Liu L, Gong W. Acta Crystallogr D Biol Crystallogr 69 830-837 (2013)
  4. Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1. Fex Svenningsen Å, Löring S, Sørensen AL, Huynh HUB, Hjæresen S, Martin N, Moeller JB, Elkjær ML, Holmskov U, Illes Z, Andersson M, Nielsen SB, Benedikz E. Cell Mol Life Sci 74 4561-4572 (2017)
  5. Functional analysis and cryo-electron microscopy of Campylobacter jejuni serine protease HtrA. Zarzecka U, Grinzato A, Kandiah E, Cysewski D, Berto P, Skorko-Glonek J, Zanotti G, Backert S. Gut Microbes 12 1-16 (2020)
  6. Allosteric inhibition of HTRA1 activity by a conformational lock mechanism to treat age-related macular degeneration. Gerhardy S, Ultsch M, Tang W, Green E, Holden JK, Li W, Estevez A, Arthur C, Tom I, Rohou A, Kirchhofer D. Nat Commun 13 5222 (2022)


Reviews citing this publication (15)

  1. HTRA proteases: regulated proteolysis in protein quality control. Clausen T, Kaiser M, Huber R, Ehrmann M. Nat Rev Mol Cell Biol 12 152-162 (2011)
  2. New approaches for dissecting protease functions to improve probe development and drug discovery. Deu E, Verdoes M, Bogyo M. Nat Struct Mol Biol 19 9-16 (2012)
  3. Architecture and regulation of HtrA-family proteins involved in protein quality control and stress response. Hansen G, Hilgenfeld R. Cell Mol Life Sci 70 761-775 (2013)
  4. Amyloid assembly and disassembly. Chuang E, Hori AM, Hesketh CD, Shorter J. J Cell Sci 131 jcs189928 (2018)
  5. Features of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy. Nozaki H, Nishizawa M, Onodera O. Stroke 45 3447-3453 (2014)
  6. The emerging roles of HTRA1 in musculoskeletal disease. Tiaden AN, Richards PJ. Am J Pathol 182 1482-1488 (2013)
  7. HTRA1-Related Cerebral Small Vessel Disease: A Review of the Literature. Uemura M, Nozaki H, Kato T, Koyama A, Sakai N, Ando S, Kanazawa M, Hishikawa N, Nishimoto Y, Polavarapu K, Nalini A, Hanazono A, Kuzume D, Shindo A, El-Ghanem M, Abe A, Sato A, Yoshida M, Ikeuchi T, Mizuta I, Mizuno T, Onodera O. Front Neurol 11 545 (2020)
  8. Surface loops of trypsin-like serine proteases as determinants of function. Goettig P, Brandstetter H, Magdolen V. Biochimie 166 52-76 (2019)
  9. Lysyl oxidases: linking structures and immunity in the tumor microenvironment. Tenti P, Vannucci L. Cancer Immunol Immunother 69 223-235 (2020)
  10. Molecular structure and the role of high-temperature requirement protein 1 in skeletal disorders and cancers. Li Y, Yuan J, Rothzerg E, Wu X, Xu H, Zhu S, Xu J. Cell Prolif 53 e12746 (2020)
  11. Genotype-phenotype correlations of heterozygous HTRA1-related cerebral small vessel disease: case report and systematic review. Zhang H, Qin X, Shi Y, Gao X, Wang F, Wang H, Shang J, Zhao J, Zhang J, Shao F. Neurogenetics 22 187-194 (2021)
  12. Overview of Human HtrA Family Proteases and Their Distinctive Physiological Roles and Unique Involvement in Diseases, Especially Cancer and Pregnancy Complications. Wang Y, Nie G. Int J Mol Sci 22 10756 (2021)
  13. Are apolipoprotein E fragments a promising new therapeutic target for Alzheimer's disease? Vecchio FL, Bisceglia P, Imbimbo BP, Lozupone M, Latino RR, Resta E, Leone M, Solfrizzi V, Greco A, Daniele A, Watling M, Panza F, Seripa D. Ther Adv Chronic Dis 13 20406223221081605 (2022)
  14. Report of two pedigrees with heterozygous HTRA1 variants-related cerebral small vessel disease and literature review. Zhou H, Jiao B, Ouyang Z, Wu Q, Shen L, Fang L. Mol Genet Genomic Med 10 e2032 (2022)
  15. Heterozygous Pathogenic and Likely Pathogenic Symptomatic HTRA1 Variant Carriers in Cerebral Small Vessel Disease. Xu SY, Li HJ, Li S, Ren QQ, Liang JL, Li CX. Int J Gen Med 16 1149-1162 (2023)

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  1. Determinants of amyloid fibril degradation by the PDZ protease HTRA1. Poepsel S, Sprengel A, Sacca B, Kaschani F, Kaiser M, Gatsogiannis C, Raunser S, Clausen T, Ehrmann M. Nat Chem Biol 11 862-869 (2015)
  2. Structural and functional analysis of HtrA1 and its subdomains. Eigenbrot C, Ultsch M, Lipari MT, Moran P, Lin SJ, Ganesan R, Quan C, Tom J, Sandoval W, van Lookeren Campagne M, Kirchhofer D. Structure 20 1040-1050 (2012)
  3. Human high temperature requirement serine protease A1 (HTRA1) degrades tau protein aggregates. Tennstaedt A, Pöpsel S, Truebestein L, Hauske P, Brockmann A, Schmidt N, Irle I, Sacca B, Niemeyer CM, Brandt R, Ksiezak-Reding H, Tirniceriu AL, Egensperger R, Baldi A, Dehmelt L, Kaiser M, Huber R, Clausen T, Ehrmann M. J Biol Chem 287 20931-20941 (2012)
  4. Detrimental role for human high temperature requirement serine protease A1 (HTRA1) in the pathogenesis of intervertebral disc (IVD) degeneration. Tiaden AN, Klawitter M, Lux V, Mirsaidi A, Bahrenberg G, Glanz S, Quero L, Liebscher T, Wuertz K, Ehrmann M, Richards PJ. J Biol Chem 287 21335-21345 (2012)
  5. Shark Attack: high affinity binding proteins derived from shark vNAR domains by stepwise in vitro affinity maturation. Zielonka S, Weber N, Becker S, Doerner A, Christmann A, Christmann C, Uth C, Fritz J, Schäfer E, Steinmann B, Empting M, Ockelmann P, Lierz M, Kolmar H. J Biotechnol 191 236-245 (2014)
  6. Molecular adaptation of the DegQ protease to exert protein quality control in the bacterial cell envelope. Sawa J, Malet H, Krojer T, Canellas F, Ehrmann M, Clausen T. J Biol Chem 286 30680-30690 (2011)
  7. Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ. Malet H, Canellas F, Sawa J, Yan J, Thalassinos K, Ehrmann M, Clausen T, Saibil HR. Nat Struct Mol Biol 19 152-157 (2012)
  8. Composition and proteolytic processing of corneal deposits associated with mutations in the TGFBI gene. Karring H, Runager K, Thøgersen IB, Klintworth GK, Højrup P, Enghild JJ. Exp Eye Res 96 163-170 (2012)
  9. Lysyl oxidase drives tumour progression by trapping EGF receptors at the cell surface. Tang H, Leung L, Saturno G, Viros A, Smith D, Di Leva G, Morrison E, Niculescu-Duvaz D, Lopes F, Johnson L, Dhomen N, Springer C, Marais R. Nat Commun 8 14909 (2017)
  10. Proteolytic Degradation and Inflammation Play Critical Roles in Polypoidal Choroidal Vasculopathy. Kumar S, Nakashizuka H, Jones A, Lambert A, Zhao X, Shen M, Parker M, Wang S, Berriochoa Z, Fnu A, VanBeuge S, Chévez-Barrios P, Tso M, Rainier J, Fu Y. Am J Pathol 187 2841-2857 (2017)
  11. Serine protease HtrA1 accumulates in corneal transforming growth factor beta induced protein (TGFBIp) amyloid deposits. Karring H, Poulsen ET, Runager K, Thøgersen IB, Klintworth GK, Højrup P, Enghild JJ. Mol Vis 19 861-876 (2013)
  12. Catalytic mechanism and mode of action of the periplasmic alginate epimerase AlgG. Wolfram F, Kitova EN, Robinson H, Walvoort MT, Codée JD, Klassen JS, Howell PL. J Biol Chem 289 6006-6019 (2014)
  13. Temperature-induced changes of HtrA2(Omi) protease activity and structure. Zurawa-Janicka D, Jarzab M, Polit A, Skorko-Glonek J, Lesner A, Gitlin A, Gieldon A, Ciarkowski J, Glaza P, Lubomska A, Lipinska B. Cell Stress Chaperones 18 35-51 (2013)
  14. Chromosome 10q26-driven age-related macular degeneration is associated with reduced levels of HTRA1 in human retinal pigment epithelium. Williams BL, Seager NA, Gardiner JD, Pappas CM, Cronin MC, Amat di San Filippo C, Anstadt RA, Liu J, Toso MA, Nichols L, Parnell TJ, Eve JR, Heinz S, Hayes MGB, Bartel PL, Zouache MA, Richards BT, Hageman GS. Proc Natl Acad Sci U S A 118 e2103617118 (2021)
  15. Late-onset retinal degeneration pathology due to mutations in CTRP5 is mediated through HTRA1. Chekuri A, Zientara-Rytter K, Soto-Hermida A, Borooah S, Voronchikhina M, Biswas P, Kumar V, Goodsell D, Hayward C, Shaw P, Stanton C, Garland D, Subramani S, Ayyagari R. Aging Cell 18 e13011 (2019)
  16. The salt-sensitive structure and zinc inhibition of Borrelia burgdorferi protease BbHtrA. Russell TM, Tang X, Goldstein JM, Bagarozzi D, Johnson BJ. Mol Microbiol 99 586-596 (2016)
  17. Oligomeric assembly regulating mitochondrial HtrA2 function as examined by methyl-TROSY NMR. Toyama Y, Harkness RW, Lee TYT, Maynes JT, Kay LE. Proc Natl Acad Sci U S A 118 e2025022118 (2021)
  18. Alpha-1-antitrypsin: a novel human high temperature requirement protease A1 (HTRA1) substrate in human placental tissue. Frochaux V, Hildebrand D, Talke A, Linscheid MW, Schlüter H. PLoS One 9 e109483 (2014)
  19. Ebola virus envelope glycoprotein derived peptide in human Furin-bound state: computational studies. Omotuyi IO. J Biomol Struct Dyn 33 461-470 (2015)
  20. HTRA1 Mutations Identified in Symptomatic Carriers Have the Property of Interfering the Trimer-Dependent Activation Cascade. Uemura M, Nozaki H, Koyama A, Sakai N, Ando S, Kanazawa M, Kato T, Onodera O. Front Neurol 10 693 (2019)
  21. Magnetite Biomineralization in Magnetospirillum magneticum Is Regulated by a Switch-like Behavior in the HtrA Protease MamE. Hershey DM, Browne PJ, Iavarone AT, Teyra J, Lee EH, Sidhu SS, Komeili A. J Biol Chem 291 17941-17952 (2016)
  22. The autolysis of human HtrA1 is governed by the redox state of its N-terminal domain. Risør MW, Poulsen ET, Thomsen LR, Dyrlund TF, Nielsen TA, Nielsen NC, Sanggaard KW, Enghild JJ. Biochemistry 53 3851-3857 (2014)
  23. Two novel heterozygous HTRA1 mutations in two pedigrees with cerebral small vessel disease families. Zhang WY, Xie F, Lu PL. Neurol Sci 39 497-501 (2018)
  24. HtrA1 Mediated Intracellular Effects on Tubulin Using a Polarized RPE Disease Model. Melo E, Oertle P, Trepp C, Meistermann H, Burgoyne T, Sborgi L, Cabrera AC, Chen CY, Hoflack JC, Kam-Thong T, Schmucki R, Badi L, Flint N, Ghiani ZE, Delobel F, Stucki C, Gromo G, Einhaus A, Hornsperger B, Golling S, Siebourg-Polster J, Gerber F, Bohrmann B, Futter C, Dunkley T, Hiller S, Schilling O, Enzmann V, Fauser S, Plodinec M, Iacone R. EBioMedicine 27 258-274 (2018)
  25. The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation. Stuqui B, Conceição AL, Termini L, Sichero L, Villa LL, Rahal P, Calmon MF. BMC Cancer 16 840 (2016)
  26. The serine protease HtrA1 contributes to the formation of an extracellular 25-kDa apolipoprotein E fragment that stimulates neuritogenesis. Muñoz SS, Li H, Ruberu K, Chu Q, Saghatelian A, Ooi L, Garner B. J Biol Chem 293 4071-4084 (2018)
  27. Chemical biology approaches reveal conserved features of a C-terminal processing PDZ protease. Weski J, Meltzer M, Spaan L, Mönig T, Oeljeklaus J, Hauske P, Vouilleme L, Volkmer R, Boisguerin P, Boyd D, Huber R, Kaiser M, Ehrmann M. Chembiochem 13 402-408 (2012)
  28. HTRA1-related autosomal dominant cerebral small vessel disease. Liu JY, Zhu YC, Zhou LX, Wei YP, Mao CH, Cui LY, Peng B, Yao M. Chin Med J (Engl) 134 178-184 (2020)
  29. The Chlamydomonas deg1c Mutant Accumulates Proteins Involved in High Light Acclimation. Theis J, Lang J, Spaniol B, Ferté S, Niemeyer J, Sommer F, Zimmer D, Venn B, Mehr SF, Mühlhaus T, Wollman FA, Schroda M. Plant Physiol 181 1480-1497 (2019)
  30. The first Greek case of heterozygous cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy: An atypical clinico-radiological presentation. Bougea A, Velonakis G, Spantideas N, Anagnostou E, Paraskevas G, Kapaki E, Kararizou E. Neuroradiol J 30 583-585 (2017)
  31. Distinct Contribution of the HtrA Protease and PDZ Domains to Its Function in Stress Resilience and Virulence of Bacillus anthracis. Israeli M, Elia U, Rotem S, Cohen H, Tidhar A, Bercovich-Kinori A, Cohen O, Chitlaru T. Front Microbiol 10 255 (2019)
  32. Tailored Ahp-cyclodepsipeptides as Potent Non-covalent Serine Protease Inhibitors. Köcher S, Rey J, Bongard J, Tiaden AN, Meltzer M, Richards PJ, Ehrmann M, Kaiser M. Angew Chem Int Ed Engl 56 8555-8558 (2017)
  33. Activity-modulating monoclonal antibodies to the human serine protease HtrA3 provide novel insights into regulating HtrA proteolytic activities. Singh H, Nero TL, Wang Y, Parker MW, Nie G. PLoS One 9 e108235 (2014)
  34. Distinct 3D Architecture and Dynamics of the Human HtrA2(Omi) Protease and Its Mutated Variants. Gieldon A, Zurawa-Janicka D, Jarzab M, Wenta T, Golik P, Dubin G, Lipinska B, Ciarkowski J. PLoS One 11 e0161526 (2016)
  35. HtrA4 Protease Promotes Chemotherapeutic-Dependent Cancer Cell Death. Wenta T, Rychlowski M, Jarzab M, Lipinska B. Cells 8 E1112 (2019)
  36. Activation by substoichiometric inhibition. Merdanovic M, Burston SG, Schmitz AL, Köcher S, Knapp S, Clausen T, Kaiser M, Huber R, Ehrmann M. Proc Natl Acad Sci U S A 117 1414-1418 (2020)
  37. ER stress-induced aggresome trafficking of HtrA1 protects against proteotoxicity. Gerhardt MJ, Marsh JA, Morrison M, Kazlauskas A, Khadka A, Rosenkranz S, DeAngelis MM, Saint-Geniez M, Jacobo SMP. J Mol Cell Biol 9 516-532 (2017)
  38. Molecular motion regulates the activity of the Mitochondrial Serine Protease HtrA2. Merski M, Moreira C, Abreu RM, Ramos MJ, Fernandes PA, Martins LM, Pereira PJB, Macedo-Ribeiro S. Cell Death Dis 8 e3119 (2017)
  39. Protoporphyrins enhance oligomerization and enzymatic activity of HtrA1 serine protease. Jo H, Patterson V, Stoessel S, Kuan CY, Hoh J. PLoS One 9 e115362 (2014)
  40. Cerebral Small Vessel Disease Related to a Heterozygous Nonsense Mutation in HTRA1. Ohta K, Ozawa T, Fujinaka H, Goto K, Nakajima T. Intern Med 59 1309-1313 (2020)
  41. A distinct concerted mechanism of structural dynamism defines activity of human serine protease HtrA3. Acharya S, Dutta S, Bose K. Biochem J 477 407-429 (2020)
  42. Ahp cyclodepsipeptides: the impact of the Ahp residue on the "canonical inhibition" of S1 serine proteases. Stolze SC, Meltzer M, Ehrmann M, Kaiser M. Chembiochem 14 1301-1308 (2013)
  43. The crystal structure of Deg9 reveals a novel octameric-type HtrA protease. Ouyang M, Li X, Zhao S, Pu H, Shen J, Adam Z, Clausen T, Zhang L, Zhang L. Nat Plants 3 973-982 (2017)
  44. Novel In-Frame Deletion in HTRA1 Gene, Responsible for Stroke at a Young Age and Dementia-A Case Study. Grigaitė J, Šiaurytė K, Audronytė E, Preikšaitienė E, Burnytė B, Pranckevičienė E, Ekkert A, Utkus A, Jatužis D. Genes (Basel) 12 1955 (2021)
  45. Peptide selectivity between the PDZ domains of human pregnancy-related serine proteases (HtrA1, HtrA2, HtrA3, and HtrA4) can be reshaped by different halogen probes. Sun ML, Sun LM, Wang YQ. J Mol Recognit 31 e2698 (2018)
  46. Novel mutations in HTRA1-related cerebral small vessel disease and comparison with CADASIL. Zhang C, Zheng H, Li X, Li S, Li W, Wang Z, Niu S, Wang X, Zhang Z. Ann Clin Transl Neurol 9 1586-1595 (2022)
  47. An allosteric HTRA1-calpain 2 complex with restricted activation profile. Rey J, Breiden M, Lux V, Bluemke A, Steindel M, Ripkens K, Möllers B, Bravo Rodriguez K, Boisguerin P, Volkmer R, Mieres-Perez J, Clausen T, Sanchez-Garcia E, Ehrmann M. Proc Natl Acad Sci U S A 119 e2113520119 (2022)
  48. Clinical features and pathogenicity assessment in patients with HTRA1-autosomal dominant disease. He Z, Wang L, Zhang Y, Yin C, Niu Y. Neurol Sci 44 639-647 (2023)
  49. Novel Heterozygous HTRA1 Pathogenic Variant Found in a Chinese Family with Autosomal Dominant Cerebral Small Vessel Disease. Wu C, Chen L, Ke S. Ann Indian Acad Neurol 23 832-835 (2020)
  50. Letter Reply to: "Inappropriate interpretation of non-pathogenic HTRA1 variant as pathogenic". Zhang C, Zheng H, Li X, Li S, Li W, Wang Z, Niu S, Wang X, Zhang Z. Ann Clin Transl Neurol 10 1263 (2023)
  51. Structural basis of DegP protease temperature-dependent activation. Šulskis D, Thoma J, Burmann BM. Sci Adv 7 eabj1816 (2021)
  52. Structural basis of protein substrate processing by human mitochondrial high-temperature requirement A2 protease. Toyama Y, Harkness RW, Kay LE. Proc Natl Acad Sci U S A 119 e2203172119 (2022)
  53. TGF-β/Smad Signalling Activation by HTRA1 Regulates the Function of Human Lens Epithelial Cells and Its Mechanism in Posterior Subcapsular Congenital Cataract. Lin X, Yang T, Liu X, Fan F, Zhou X, Li H, Luo Y. Int J Mol Sci 23 14431 (2022)
  54. The HhoA protease from Synechocystis sp. PCC 6803 - Novel insights into structure and activity regulation. Hall M, Wagner R, Lam XT, Funk C, Persson K. J Struct Biol 198 147-153 (2017)


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