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Tim Clausen

Our group employs an integrative Structural Biology approach to study complex proteases and chaperones that function as safeguards in the cell, preventing other proteins from undergoing dangerous interactions. By addressing mechanistic details of the protein-quality-control machinery, we aim to develop strategies against misbehaving proteins connected with neurodegenerative diseases, inclusion body myopathies, cancer and ageing. Moreover, differences in the protein folding and protein degradation pathways between bacterial pathogens and their hosts will guide the development of novel antibiotics.

Publications

2025

Carrillo Roas, S., Yagita, Y., Murphy, P., Kurzbauer, R., Clausen, T., Zavodszky, E., Hegde, RS. (2025)

Convergence of orphan quality control pathways at a ubiquitin chain-elongating ligase.

Corresponding preprint Mol Cell. 85(4):815-828.e10
Ahel, J., Balci, A., Faas, V., Grabarczyk, DB., Harmo, R., Squair, DR., Zhang, J., Roitinger, E., Lamoliatte, F., Mathur, S., Deszcz, L., Bell, LE., Lehner, A., Williams, TL., Sowar, H., Meinhart, A., Wood, NT., Clausen, T., Virdee, S., Fletcher, AJ. (2025)

ATP functions as a pathogen-associated molecular pattern to activate the E3 ubiquitin ligase RNF213.

Nat Commun. 16(1):4414
Grabarczyk, DB., Aird, EJ., Reznikow, V., Kirchgatterer, PC., Ehrmann, JF., Kurzbauer, R., Bell, LE., Kellner, MJ., Aggarwal, R., Schleiffer, A., Faas, V., Deszcz, L., Meinhart, A., Versteeg, GA., Penninger, JM., Stelzl, LS., Gaidt, MM., Tessmer, I., Corn, JE., Clausen, T. (2025)

A split-site E3 ligase mechanism enables ZNFX1 to ubiquitinate and cluster single-stranded RNA into ubiquitin-coated nucleoprotein particles.

Cell.
Grabarczyk, DB., Ehrmann, JF., Murphy, P., Yang, WS., Kurzbauer, R., Bell, LE., Deszcz, L., Neuhold, J., Schleiffer, A., Shulkina, A., Lee, J., Shin, JS., Meinhart, A., Versteeg, GA., Zavodszky, E., Song, HK., Hegde, RS., Clausen, T. (2025)

Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.

Science. 389(6763):909-914
Shulkina, A., Hacker, K., Ehrmann, JF., Budroni, V., Mandlbauer, A., Bock, J., Grabarczyk, DB., Edobor, G., Cochella, L., Clausen, T., Versteeg, GA. (2025)

TRIM52 maintains cellular fitness and is under tight proteolytic control by multiple giant E3 ligases.

Nat Commun. 16(1):3894

2024

Junk, L., Schmiedel, VM., Guha, S., Fischel, K., Greb, P., Vill, K., Krisilia, V., van Geelen, L., Rumpel, K., Kaur, P., Krishnamurthy, RV., Narayanan, S., Shandil, RK., Singh, M., Kofink, C., Mantoulidis, A., Biber, P., Gmaschitz, G., Kazmaier, U., Meinhart, A., Leodolter, J., Hoi, D., Junker, S., Morreale, FE., Clausen, T., Kalscheuer, R., Weinstabl, H., Boehmelt, G. (2024)

Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria.

Nat Commun. 15(1):2005
Vogel, A., Arnese, R., Gudino Carrillo, RM., Sehr, D., Deszcz, L., Bylicki, A., Meinhart, A., Clausen, T. (2024)

UNC-45 assisted myosin folding depends on a conserved FX3HY motif implicated in Freeman Sheldon Syndrome.

Nat Commun. 15(1):6272
Beaufort, N., Ingendahl, L., Merdanovic, M., Schmidt, A., Podlesainski, D., Richter, T., Neumann, T., Kuszner, M., Vetter, IR., Stege, P., Burston, SG., Filipovic, A., Ruiz-Blanco, YB., Bravo-Rodriguez, K., Mieres-Perez, J., Beuck, C., Uebel, S., Zobawa, M., Schillinger, J., Malik, R., Todorov-Völgyi, K., Rey, J., Roberti, A., Hagemeier, B., Wefers, B., Müller, SA., Wurst, W., Sanchez-Garcia, E., Zimmermann, A., Hu, XY., Clausen, T., Huber, R., Lichtenthaler, SF., Schmuck, C., Giese, M., Kaiser, M., Ehrmann, M., Dichgans, M. (2024)

Rational correction of pathogenic conformational defects in HTRA1.

Nat Commun. 15(1):5944
Pre-printShulkina, A., Hacker, K., Ehrmann, J. F., Budroni, V., Mandlbauer, A., Bock, J., Grabarczyk, D. B., Cochella, L., Clausen, T., Versteeg, G.A. (2024)

TRIM52 is a primate-specific player in the DNA repair process under tight proteolytic control by a triad of giant E3 ligases

bioRxiv. 10.1101/2024.05.16.594269
Pre-printSchwartz, I. Budroni, V., Meyenberg, M., Hornegger H., Hacker, K., Schwartz, S., Hodakova, Z., Grabarczyk, D. B., Ehrmann, J. F., Scinicariello, S., Haselbach, D., Menche, J., Clausen, T., Karagöz, G. E., Versteeg, G. A. (2024)

Multiple ubiquitin ligases protect human genome integrity by targeting cancer-associated APOBEC3 deaminases for degradation

bioRxiv. 10.1101/2024.04.23.590688
Pre-printSchwartz I, Budroni V, Meyenberg M, Hornegger H, Hacker K, Schwartz S, Hodakova Z, Grabarczyk DB, Ehrmann JF , Scinicariello S, Haselbach D, Menche J, Clausen T, Karagöz E, Versteeg GA (2024)

Guardian ubiquitin E3 ligases target cancer-associated APOBEC3 deaminases for degradation to promote human genome integrity

bioRxiv. 2024.04.23.590688

2023

Ehrmann, JF., Grabarczyk, DB., Heinke, M., Deszcz, L., Kurzbauer, R., Hudecz, O., Shulkina, A., Gogova, R., Meinhart, A., Versteeg, GA., Clausen, T. (2023)

Structural basis for regulation of apoptosis and autophagy by the BIRC6/SMAC complex.

Science. 379(6637):1117-1123
Picchianti, L., Sánchez de Medina Hernández, V., Zhan, N., Irwin, NA., Groh, R., Stephani, M., Hornegger, H., Beveridge, R., Sawa-Makarska, J., Lendl, T., Grujic, N., Naumann, C., Martens, S., Richards, TA., Clausen, T., Ramundo, S., Karagöz, GE., Dagdas, Y. (2023)

Shuffled ATG8 interacting motifs form an ancestral bridge between UFMylation and autophagy.

EMBO J. :e112053
Scinicariello, S., Soderholm, A., Schäfer, M., Shulkina, A., Schwartz, I., Hacker, K., Gogova, R., Kalis, R., Froussios, K., Budroni, V., Bestehorn, A., Clausen, T., Kovarik, P., Zuber, J., Versteeg, GA. (2023)

HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation.

Corresponding preprint Elife. 12
Hoi, DM., Junker, S., Junk, L., Schwechel, K., Fischel, K., Podlesainski, D., Hawkins, PME., van Geelen, L., Kaschani, F., Leodolter, J., Morreale, FE., Kleine, S., Guha, S., Rumpel, K., Schmiedel, VM., Weinstabl, H., Meinhart, A., Payne, RJ., Kaiser, M., Hartl, M., Boehmelt, G., Kazmaier, U., Kalscheuer, R., Clausen, T. (2023)

Clp-targeting BacPROTACs impair mycobacterial proteostasis and survival.

Cell. 186(10):2176-2192.e22

2022

Morreale, FE., Kleine, S., Leodolter, J., Junker, S., Hoi, DM., Ovchinnikov, S., Okun, A., Kley, J., Kurzbauer, R., Junk, L., Guha, S., Podlesainski, D., Kazmaier, U., Boehmelt, G., Weinstabl, H., Rumpel, K., Schmiedel, VM., Hartl, M., Haselbach, D., Meinhart, A., Kaiser, M., Clausen, T. (2022)

BacPROTACs mediate targeted protein degradation in bacteria.

Corresponding preprint Cell. 185(13):2338-2353.e18
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. (2022)

An allosteric HTRA1-calpain 2 complex with restricted activation profile.

Proc Natl Acad Sci U S A. 119(14):e2113520119
Ihara, M., Yamamoto, Y., Hattori, Y., Liu, W., Kobayashi, H., Ishiyama, H., Yoshimoto, T., Miyawaki, S., Clausen, T., Bang, OY., Steinberg, GK., Tournier-Lasserve, E., Koizumi, A. (2022)

Moyamoya disease: diagnosis and interventions.

Lancet Neurol.
Cable, J., Weber-Ban, E., Clausen, T., Walters, KJ., Sharon, M., Finley, DJ., Gu, Y., Hanna, J., Feng, Y., Martens, S., Simonsen, A., Hansen, M., Zhang, H., Goodwin, JM., Reggio, A., Chang, C., Ge, L., Schulman, BA., Deshaies, RJ., Dikic, I., Harper, JW., Wertz, IE., Thomä, NH., Słabicki, M., Frydman, J., Jakob, U., David, DC., Bennett, EJ., Bertozzi, CR., Sardana, R., Eapen, VV., Carra, S. (2022)

Targeted protein degradation: from small molecules to complex organelles-a Keystone Symposia report.

Ann N Y Acad Sci. 1510(1):79-99
Hawkins, PME., Hoi, DM., Cheung, CY., Wang, T., Quan, D., Sasi, VM., Liu, DY., Linington, RG., Jackson, CJ., Oehlers, SH., Cook, GM., Britton, WJ., Clausen, T., Payne, RJ. (2022)

Potent Bactericidal Antimycobacterials Targeting the Chaperone ClpC1 Based on the Depsipeptide Natural Products Ecumicin and Ohmyungsamycin A.

J Med Chem. 65(6):4893-4908

2021

Asanović, I., Strandback, E., Kroupova, A., Pasajlic, D., Meinhart, A., Tsung-Pin, P., Djokovic, N., Anrather, D., Schuetz, T., Suskiewicz, MJ., Sillamaa, S., Köcher, T., Beveridge, R., Nikolic, K., Schleiffer, A., Jinek, M., Hartl, M., Clausen, T., Penninger, J., Macheroux, P., Weitzer, S., Martinez, J. (2021)

The oxidoreductase PYROXD1 uses NAD(P)+ as an antioxidant to sustain tRNA ligase activity in pre-tRNA splicing and unfolded protein response.

Mol Cell. 81(12):2520-2532.e16
Pre-printAhel J, Fletcher A, Grabarczyk DB, Roitinger E, Deszcz L, Lehner A, Virdee S, Clausen T. (2021)

E3 ubiquitin ligase RNF213 employs a non-canonical zinc finger active site and is allosterically regulated by ATP

bioRxiv. 2021.05.10.443411
Yelagandula, R., Bykov, A., Vogt, A., Heinen, R., Özkan, E., Strobl, MM., Baar, JC., Uzunova, K., Hajdusits, B., Kordic, D., Suljic, E., Kurtovic-Kozaric, A., Izetbegovic, S., Schaeffer, J., Hufnagl, P., Zoufaly, A., Seitz, T., Födinger, M., Allerberger, F., Stark, A., Cochella, L., Elling, U. (2021)

Multiplexed detection of SARS-CoV-2 and other respiratory infections in high throughput by SARSeq.

Nat Commun. 12(1):3132
Rodriguez Carvajal, A., Grishkovskaya, I., Gomez Diaz, C., Vogel, A., Sonn-Segev, A., Kushwah, MS., Schodl, K., Deszcz, L., Orban-Nemeth, Z., Sakamoto, S., Mechtler, K., Kukura, P., Clausen, T., Haselbach, D., Ikeda, F. (2021)

The linear ubiquitin chain assembly complex (LUBAC) generates heterotypic ubiquitin chains.

Corresponding preprint Elife. 10
Hajdusits, B., Suskiewicz, MJ., Hundt, N., Meinhart, A., Kurzbauer, R., Leodolter, J., Kukura, P., Clausen, T. (2021)

McsB forms a gated kinase chamber to mark aberrant bacterial proteins for degradation.

Corresponding preprint Elife. 10
Grabarczyk, DB., Petrova, OA., Deszcz, L., Kurzbauer, R., Murphy, P., Ahel, J., Vogel, A., Gogova, R., Faas, V., Kordic, D., Schleiffer, A., Meinhart, A., Imre, R., Lehner, A., Neuhold, J., Bader, G., Stolt-Bergner, P., Böttcher, J., Wolkerstorfer, B., Fischer, G., Grishkovskaya, I., Haselbach, D., Kessler, D., Clausen, T. (2021)

HUWE1 employs a giant substrate-binding ring to feed and regulate its HECT E3 domain.

Nat Chem Biol.

2020

Ahel, J., Lehner, A., Vogel, A., Schleiffer, A., Meinhart, A., Haselbach, D., Clausen, T. (2020)

Moyamoya disease factor RNF213 is a giant E3 ligase with a dynein-like core and a distinct ubiquitin-transfer mechanism.

Elife. 9
Merdanovic, M., Burston, SG., Schmitz, AL., Köcher, S., Knapp, S., Clausen, T., Kaiser, M., Huber, R., Ehrmann, M. (2020)

Activation by substoichiometric inhibition.

Proc Natl Acad Sci U S A. 117(3):1414-1418
Stephani, M., Picchianti, L., Gajic, A., Beveridge, R., Skarwan, E., Sanchez de Medina Hernandez, V., Mohseni, A., Clavel, M., Zeng, Y., Naumann, C., Matuszkiewicz, M., Turco, E., Loefke, C., Li, B., Dürnberger, G., Schutzbier, M., Chen, HT., Abdrakhmanov, A., Savova, A., Chia, KS., Djamei, A., Schaffner, I., Abel, S., Jiang, L., Mechtler, K., Ikeda, F., Martens, S., Clausen, T., Dagdas, Y. (2020)

A cross-kingdom conserved ER-phagy receptor maintains endoplasmic reticulum homeostasis during stress.

Elife. 9
Beveridge, R., Kessler, D., Rumpel, K., Ettmayer, P., Meinhart, A., Clausen, T. (2020)

Native Mass Spectrometry Can Effectively Predict PROTAC Efficacy.

ACS Cent Sci. 6(7):1223-1230

2019

Suskiewicz, MJ., Hajdusits, B., Beveridge, R., Heuck, A., Vu, LD., Kurzbauer, R., Hauer, K., Thoeny, V., Rumpel, K., Mechtler, K., Meinhart, A., Clausen, T. (2019)

Structure of McsB, a protein kinase for regulated arginine phosphorylation.

Nat Chem Biol. 15(5):510-518
Hnia, K., Clausen, T., Moog-Lutz, C. (2019)

Shaping Striated Muscles with Ubiquitin Proteasome System in Health and Disease.

Trends Mol Med. 25(9):760-774
Hellerschmied, D., Lehner, A., Franicevic, N., Arnese, R., Johnson, C., Vogel, A., Meinhart, A., Kurzbauer, R., Deszcz, L., Gazda, L., Geeves, M., Clausen, T. (2019)

Molecular features of the UNC-45 chaperone critical for binding and folding muscle myosin.

Nat Commun. 10(1):4781

2018

Hellerschmied, D., Roessler, M., Lehner, A., Gazda, L., Stejskal, K., Imre, R., Mechtler, K., Dammermann, A., Clausen, T. (2018)

UFD-2 is an adaptor-assisted E3 ligase targeting unfolded proteins.

Nat Commun. 9(1):484

2017

Ouyang, M., Li, X., Zhao, S., Pu, H., Shen, J., Adam, Z., Clausen, T., Zhang, L. (2017)

The crystal structure of Deg9 reveals a novel octameric-type HtrA protease.

Nat Plants. 3(12):973-982

2016

Suskiewicz, MJ., Clausen, T. (2016)

Chemical Biology Interrogates Protein Arginine Phosphorylation.

Cell Chem Biol. 23(8):888-90
Trentini, DB., Suskiewicz, MJ., Heuck, A., Kurzbauer, R., Deszcz, L., Mechtler, K., Clausen, T. (2016)

Arginine phosphorylation marks proteins for degradation by a Clp protease.

Nature. 539(7627):48-53
Gallego, LD., Ghodgaonkar Steger, M., Polyansky, AA., Schubert, T., Zagrovic, B., Zheng, N., Clausen, T., Herzog, F., Köhler, A. (2016)

Structural mechanism for the recognition and ubiquitination of a single nucleosome residue by Rad6-Bre1.

Proc Natl Acad Sci U S A. 113(38):10553-8
Heuck, A., Schitter-Sollner, S., Suskiewicz, MJ., Kurzbauer, R., Kley, J., Schleiffer, A., Rombaut, P., Herzog, F., Clausen, T. (2016)

Structural basis for the disaggregase activity and regulation of Hsp104.

Elife. 5

2015

Schneider, M., Hellerschmied, D., Schubert, T., Amlacher, S., Vinayachandran, V., Reja, R., Pugh, BF., Clausen, T., Köhler, A. (2015)

The Nuclear Pore-Associated TREX-2 Complex Employs Mediator to Regulate Gene Expression.

Cell. 162(5):1016-28
Poepsel, S., Sprengel, A., Sacca, B., Kaschani, F., Kaiser, M., Gatsogiannis, C., Raunser, S., Clausen, T., Ehrmann, M. (2015)

Determinants of amyloid fibril degradation by the PDZ protease HTRA1.

Nat Chem Biol. 11(11):862-9

2014

Dikfidan, A., Loll, B., Zeymer, C., Magler, I., Clausen, T., Meinhart, A. (2014)

RNA specificity and regulation of catalysis in the eukaryotic polynucleotide kinase Clp1.

Mol Cell. 54(6):975-86
Schmidt, A., Trentini, DB., Spiess, S., Fuhrmann, J., Ammerer, G., Mechtler, K., Clausen, T. (2014)

Quantitative phosphoproteomics reveals the role of protein arginine phosphorylation in the bacterial stress response.

Mol Cell Proteomics. 13(2):537-50
Karaca, E., Weitzer, S., Pehlivan, D., Shiraishi, H., Gogakos, T., Hanada, T., Jhangiani, SN., Wiszniewski, W., Withers, M., Campbell, IM., Erdin, S., Isikay, S., Franco, LM., Gonzaga-Jauregui, C., Gambin, T., Gelowani, V., Hunter, JV., Yesil, G., Koparir, E., Yilmaz, S., Brown, M., Briskin, D., Hafner, M., Morozov, P., Farazi, TA., Bernreuther, C., Glatzel, M., Trattnig, S., Friske, J., Kronnerwetter, C., Bainbridge, MN., Gezdirici, A., Seven, M., Muzny, DM., Boerwinkle, E., Ozen, M., Clausen, T., Tuschl, T., Yuksel, A., Hess, A., Gibbs, RA., Martinez, J., Penninger, JM., Lupski, JR. (2014)

Human CLP1 mutations alter tRNA biogenesis, affecting both peripheral and central nervous system function.

Cell. 157(3):636-50
Norell, D., Heuck, A., Tran-Thi, TA., Götzke, H., Jacob-Dubuisson, F., Clausen, T., Daley, DO., Braun, V., Müller, M., Fan, E. (2014)

Versatile in vitro system to study translocation and functional integration of bacterial outer membrane proteins.

Nat Commun. 5:5396
Trentini, DB., Fuhrmann, J., Mechtler, K., Clausen, T. (2014)

Chasing Phosphoarginine Proteins: Development of a Selective Enrichment Method Using a Phosphatase Trap.

Mol Cell Proteomics. 13(8):1953-64
Hellerschmied, D., Clausen, T. (2014)

Myosin chaperones.

Curr Opin Struct Biol. 25:9-15

2013

Mastny, M., Heuck, A., Kurzbauer, R., Heiduk, A., Boisguerin, P., Volkmer, R., Ehrmann, M., Rodrigues, CD., Rudner, DZ., Clausen, T. (2013)

CtpB assembles a gated protease tunnel regulating cell-cell signaling during spore formation in Bacillus subtilis.

Cell. 155(3):647-58
Fuhrmann, J., Mierzwa, B., Trentini, DB., Spiess, S., Lehner, A., Charpentier, E., Clausen, T. (2013)

Structural basis for recognizing phosphoarginine and evolving residue-specific protein phosphatases in gram-positive bacteria.

Cell Rep. 3(6):1832-9
Malvezzi, F., Litos, G., Schleiffer, A., Heuck, A., Mechtler, K., Clausen, T., Westermann, S. (2013)

A structural basis for kinetochore recruitment of the Ndc80 complex via two distinct centromere receptors.

EMBO J. 32(3):409-23
Gazda, L., Pokrzywa, W., Hellerschmied, D., Löwe, T., Forné, I., Mueller-Planitz, F., Hoppe, T., Clausen, T. (2013)

The myosin chaperone UNC-45 is organized in tandem modules to support myofilament formation in C. elegans.

Cell. 152(1-2):183-95

2012

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. (2012)

Human high temperature requirement serine protease A1 (HTRA1) degrades tau protein aggregates.

J Biol Chem. 287(25):20931-41
Dal Santo, S., Stampfl, H., Krasensky, J., Kempa, S., Gibon, Y., Petutschnig, E., Rozhon, W., Heuck, A., Clausen, T., Jonak, C. (2012)

Stress-induced GSK3 regulates the redox stress response by phosphorylating glucose-6-phosphate dehydrogenase in Arabidopsis.

Plant Cell. 24(8):3380-92
Malet, H., Canellas, F., Sawa, J., Yan, J., Thalassinos, K., Ehrmann, M., Clausen, T., Saibil, HR. (2012)

Newly folded substrates inside the molecular cage of the HtrA chaperone DegQ.

Nat Struct Mol Biol. 19(2):152-7
Breuss, M., Heng, JI., Poirier, K., Tian, G., Jaglin, XH., Qu, Z., Braun, A., Gstrein, T., Ngo, L., Haas, M., Bahi-Buisson, N., Moutard, ML., Passemard, S., Verloes, A., Gressens, P., Xie, Y., Robson, KJ., Rani, DS., Thangaraj, K., Clausen, T., Chelly, J., Cowan, NJ., Keays, DA. (2012)

Mutations in the β-tubulin gene TUBB5 cause microcephaly with structural brain abnormalities.

Cell Rep. 2(6):1554-62

2011

Sawa, J., Malet, H., Krojer, T., Canellas, F., Ehrmann, M., Clausen, T. (2011)

Molecular adaptation of the DegQ protease to exert protein quality control in the bacterial cell envelope.

J Biol Chem. 286(35):30680-30690
Kley, J., Schmidt, B., Boyanov, B., Stolt-Bergner, PC., Kirk, R., Ehrmann, M., Knopf, RR., Naveh, L., Adam, Z., Clausen, T. (2011)

Structural adaptation of the plant protease Deg1 to repair photosystem II during light exposure.

Nat Struct Mol Biol. 18(6):728-31
Clausen, T., Kaiser, M., Huber, R., Ehrmann, M. (2011)

HTRA proteases: regulated proteolysis in protein quality control.

Nat Rev Mol Cell Biol. 12(3):152-62
Truebestein, L., Tennstaedt, A., Mönig, T., Krojer, T., Canellas, F., Kaiser, M., Clausen, T., Ehrmann, M. (2011)

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

Nat Struct Mol Biol. 18(3):386-8
Merdanovic, M., Clausen, T., Kaiser, M., Huber, R., Ehrmann, M. (2011)

Protein quality control in the bacterial periplasm.

Annu Rev Microbiol. 65:149-68

2010

Sawa, J., Heuck, A., Ehrmann, M., Clausen, T. (2010)

Molecular transformers in the cell: lessons learned from the DegP protease-chaperone.

Curr Opin Struct Biol. 20(2):253-8
Hasenbein, S., Meltzer, M., Hauske, P., Kaiser, M., Huber, R., Clausen, T., Ehrmann, M. (2010)

Conversion of a regulatory into a degradative protease.

J Mol Biol. 397(4):957-66
Krojer, T., Sawa, J., Huber, R., Clausen, T. (2010)

HtrA proteases have a conserved activation mechanism that can be triggered by distinct molecular cues.

Nat Struct Mol Biol. 17(7):844-52

2009

Hauske, P., Meltzer, M., Ottmann, C., Krojer, T., Clausen, T., Ehrmann, M., Kaiser, M. (2009)

Selectivity profiling of DegP substrates and inhibitors.

Bioorg Med Chem. 17(7):2920-4
Fuhrmann, J., Schmidt, A., Spiess, S., Lehner, A., Turgay, K., Mechtler, K., Charpentier, E., Clausen, T. (2009)

McsB is a protein arginine kinase that phosphorylates and inhibits the heat-shock regulator CtsR.

Science. 324(5932):1323-7
Hauske, P., Mamant, N., Hasenbein, S., Nickel, S., Ottmann, C., Clausen, T., Ehrmann, M., Kaiser, M. (2009)

Peptidic small molecule activators of the stress sensor DegS.

Mol Biosyst. 5(9):980-5
Meltzer, M., Hasenbein, S., Mamant, N., Merdanovic, M., Poepsel, S., Hauske, P., Kaiser, M., Huber, R., Krojer, T., Clausen, T., Ehrmann, M. (2009)

Structure, function and regulation of the conserved serine proteases DegP and DegS of Escherichia coli.

Res Microbiol. 160(9):660-6
Breithaupt, C., Kurzbauer, R., Schaller, F., Stintzi, A., Schaller, A., Huber, R., Macheroux, P., Clausen, T. (2009)

Structural basis of substrate specificity of plant 12-oxophytodienoate reductases.

J Mol Biol. 392(5):1266-77
Holzmann, J., Pichler, P., Madalinski, M., Kurzbauer, R., Mechtler, K. (2009)

Stoichiometry determination of the MP1-p14 complex using a novel and cost-efficient method to produce an equimolar mixture of standard peptides.

Anal Chem. 81(24):10254-61

2008

Krojer, T., Pangerl, K., Kurt, J., Sawa, J., Stingl, C., Mechtler, K., Huber, R., Ehrmann, M., Clausen, T. (2008)

Interplay of PDZ and protease domain of DegP ensures efficient elimination of misfolded proteins.

Proc Natl Acad Sci U S A. 105(22):7702-7
Krojer, T., Sawa, J., Schäfer, E., Saibil, HR., Ehrmann, M., Clausen, T. (2008)

Structural basis for the regulated protease and chaperone function of DegP.

Nature. 453(7197):885-90
Meltzer, M., Hasenbein, S., Hauske, P., Kucz, N., Merdanovic, M., Grau, S., Beil, A., Jones, D., Krojer, T., Clausen, T., Ehrmann, M., Kaiser, M. (2008)

Allosteric activation of HtrA protease DegP by stress signals during bacterial protein quality control.

Angew Chem Int Ed Engl. 47(7):1332-4

2007

Hasselblatt, H., Kurzbauer, R., Wilken, C., Krojer, T., Sawa, J., Kurt, J., Kirk, R., Hasenbein, S., Ehrmann, M., Clausen, T. (2007)

Regulation of the sigmaE stress response by DegS: how the PDZ domain keeps the protease inactive in the resting state and allows integration of different OMP-derived stress signals upon folding stress.

Genes Dev. 21(20):2659-70

2006

Breithaupt, C., Kurzbauer, R., Lilie, H., Schaller, A., Strassner, J., Huber, R., Macheroux, P., Clausen, T. (2006)

Crystal structure of 12-oxophytodienoate reductase 3 from tomato: self-inhibition by dimerization.

Proc Natl Acad Sci U S A. 103(39):14337-42
Grau, S., Richards, PJ., Kerr, B., Hughes, C., Caterson, B., Williams, AS., Junker, U., Jones, SA., Clausen, T., Ehrmann, M. (2006)

The role of human HtrA1 in arthritic disease.

J Biol Chem. 281(10):6124-9

2005

Vietor, I., Kurzbauer, R., Brosch, G., Huber, LA. (2005)

TIS7 regulation of the beta-catenin/Tcf-4 target gene osteopontin (OPN) is histone deacetylase-dependent.

J Biol Chem. 280(48):39795-801
Kitzing, K., Fitzpatrick, TB., Wilken, C., Sawa, J., Bourenkov, GP., Macheroux, P., Clausen, T. (2005)

The 1.3 A crystal structure of the flavoprotein YqjM reveals a novel class of Old Yellow Enzymes.

J Biol Chem. 280(30):27904-13
Groll, M., Bochtler, M., Brandstetter, H., Clausen, T., Huber, R. (2005)

Molecular machines for protein degradation.

Chembiochem. 6(2):222-56
Grau, S., Baldi, A., Bussani, R., Tian, X., Stefanescu, R., Przybylski, M., Richards, P., Jones, SA., Shridhar, V., Clausen, T., Ehrmann, M. (2005)

Implications of the serine protease HtrA1 in amyloid precursor protein processing.

Proc Natl Acad Sci U S A. 102(17):6021-6

2004

Wilken, C., Kitzing, K., Kurzbauer, R., Ehrmann, M., Clausen, T. (2004)

Crystal structure of the DegS stress sensor: How a PDZ domain recognizes misfolded protein and activates a protease.

Cell. 117(4):483-94
Fitzpatrick, TB., Auweter, S., Kitzing, K., Clausen, T., Amrhein, N., Macheroux, P. (2004)

Structural and functional impairment of an Old Yellow Enzyme homologue upon affinity tag incorporation.

Protein Expr Purif. 36(2):280-91
Vadivelu, SK., Kurzbauer, R., Dieplinger, B., Zweyer, M., Schafer, R., Wernig, A., Vietor, I., Huber, LA. (2004)

Muscle regeneration and myogenic differentiation defects in mice lacking TIS7.

Mol Cell Biol. 24(8):3514-25
Kurzbauer, R., Teis, D., de Araujo, ME., Maurer-Stroh, S., Eisenhaber, F., Bourenkov, GP., Bartunik, HD., Hekman, M., Rapp, UR., Huber, LA., Clausen, T. (2004)

Crystal structure of the p14/MP1 scaffolding complex: how a twin couple attaches mitogen-activated protein kinase signaling to late endosomes.

Proc Natl Acad Sci U S A. 101(30):10984-9
Ehrmann, M., Clausen, T. (2004)

Proteolysis as a regulatory mechanism.

Annu Rev Genet. 38:709-24

2003

Groll, M., Clausen, T. (2003)

Molecular shredders: how proteasomes fulfill their role.

Curr Opin Struct Biol. 13(6):665-73
Kaiser, JT., Bruno, S., Clausen, T., Huber, R., Schiaretti, F., Mozzarelli, A., Kessler, D. (2003)

Snapshots of the cystine lyase C-DES during catalysis. Studies in solution and in the crystalline state.

J Biol Chem. 278(1):357-65

2002

Clausen, T., Southan, C., Ehrmann, M. (2002)

The HtrA family of proteases: implications for protein composition and cell fate.

Mol Cell. 10(3):443-55
Krojer, T., Garrido-Franco, M., Huber, R., Ehrmann, M., Clausen, T. (2002)

Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine.

Nature. 416(6879):455-9
Garrido-Franco, M., Laber, B., Huber, R., Clausen, T. (2002)

Enzyme-ligand complexes of pyridoxine 5'-phosphate synthase: implications for substrate binding and catalysis.

J Mol Biol. 321(4):601-12
Garrido-Franco, M., Ehlert, S., Messerschmidt, A., Marinkovic', S., Huber, R., Laber, B., Bourenkov, GP., Clausen, T. (2002)

Structure and function of threonine synthase from yeast.

J Biol Chem. 277(14):12396-405

2001

Breitinger, U., Clausen, T., Ehlert, S., Huber, R., Laber, B., Schmidt, F., Pohl, E., Messerschmidt, A. (2001)

The three-dimensional structure of cystathionine beta-lyase from Arabidopsis and its substrate specificity.

Plant Physiol. 126(2):631-42
Steegborn, C., Laber, B., Messerschmidt, A., Huber, R., Clausen, T. (2001)

Crystal structures of cystathionine gamma-synthase inhibitor complexes rationalize the increased affinity of a novel inhibitor.

J Mol Biol. 311(4):789-801
Breithaupt, C., Strassner, J., Breitinger, U., Huber, R., Macheroux, P., Schaller, A., Clausen, T. (2001)

X-ray structure of 12-oxophytodienoate reductase 1 provides structural insight into substrate binding and specificity within the family of OYE.

Structure. 9(5):419-29
Franco, MG., Laber, B., Huber, R., Clausen, T. (2001)

Structural basis for the function of pyridoxine 5'-phosphate synthase.

Structure. 9(3):245-53

2000

Steegborn, C., Clausen, T. (2000)

Specific inhibition of transsulfuration enzymes.

Rec Res Developm Biochem. 2:191-207
Garrido Franco, M., Huber, R., Schmidt, FS., Laber, B., Clausen, T. (2000)

Crystallization and preliminary X-ray crystallographic analysis of PdxJ, the pyridoxine 5'-phosphate synthesizing enzyme.

Acta Crystallogr D Biol Crystallogr. 56(Pt 8):1045-8
Clausen, T., Kaiser, JT., Steegborn, C., Huber, R., Kessler, D. (2000)

Crystal structure of the cystine C-S lyase from Synechocystis: stabilization of cysteine persulfide for FeS cluster biosynthesis.

Proc Natl Acad Sci U S A. 97(8):3856-61
Clausen, T., Schlegel, A., Peist, R., Schneider, E., Steegborn, C., Chang, YS., Haase, A., Bourenkov, GP., Bartunik, HD., Boos, W. (2000)

X-ray structure of MalY from Escherichia coli: a pyridoxal 5'-phosphate-dependent enzyme acting as a modulator in mal gene expression.

EMBO J. 19(5):831-42
Schreiber, V., Steegborn, C., Clausen, T., Boos, W., Richet, E. (2000)

A new mechanism for the control of a prokaryotic transcriptional regulator: antagonistic binding of positive and negative effectors.

Mol Microbiol. 35(4):765-76
Kaiser, JT., Clausen, T., Bourenkow, GP., Bartunik, HD., Steinbacher, S., Huber, R. (2000)

Crystal structure of a NifS-like protein from Thermotoga maritima: implications for iron sulphur cluster assembly.

J Mol Biol. 297(2):451-64

1999

Steegborn, C., Messerschmidt, A., Laber, B., Streber, W., Huber, R., Clausen, T. (1999)

The crystal structure of cystathionine gamma-synthase from Nicotiana tabacum reveals its substrate and reaction specificity.

J Mol Biol. 290(5):983-96
Steegborn, C., Clausen, T., Sondermann, P., Jacob, U., Worbs, M., Marinkovic, S., Huber, R., Wahl, MC. (1999)

Kinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration.

J Biol Chem. 274(18):12675-84
Clausen, T., Wahl, MC., Messerschmidt, A., Huber, R., Fuhrmann, JC., Laber, B., Streber, W., Steegborn, C. (1999)

Cloning, purification and characterisation of cystathionine gamma-synthase from Nicotiana tabacum.

Biol Chem. 380(10):1237-42
Laber, B., Maurer, W., Hanke, C., Gräfe, S., Ehlert, S., Messerschmidt, A., Clausen, T. (1999)

Characterization of recombinant Arabidopsis thaliana threonine synthase.

Eur J Biochem. 263(1):212-21

1998

Clausen, T., Huber, R., Prade, L., Wahl, MC., Messerschmidt, A. (1998)

Crystal structure of Escherichia coli cystathionine gamma-synthase at 1.5 A resolution.

EMBO J. 17(23):6827-38

1997

Wahl, MC., Huber, R., Prade, L., Marinkovic, S., Messerschmidt, A., Clausen, T. (1997)

Cloning, purification, crystallization, and preliminary X-ray diffraction analysis of cystathionine gamma-synthase from E. coli.

FEBS Lett. 414(3):492-6
Jacob, U., Mack, M., Clausen, T., Huber, R., Buckel, W., Messerschmidt, A. (1997)

Glutaconate CoA-transferase from Acidaminococcus fermentans: the crystal structure reveals homology with other CoA-transferases.

Structure. 5(3):415-26
Clausen, T., Laber, B., Messerschmidt, A. (1997)

Mode of action of cystathionine beta-lyase.

Biol Chem. 378(3-4):321-6
Clausen, T., Huber, R., Messerschmidt, A., Pohlenz, HD., Laber, B. (1997)

Slow-binding inhibition of Escherichia coli cystathionine beta-lyase by L-aminoethoxyvinylglycine: a kinetic and X-ray study.

Biochemistry. 36(41):12633-43

1996

Laber, B., Clausen, T., Huber, R., Messerschmidt, A., Egner, U., Müller-Fahrnow, A., Pohlenz, HD. (1996)

Cloning, purification, and crystallization of Escherichia coli cystathionine beta-lyase.

FEBS Lett. 379(1):94-6
Clausen, T., Huber, R., Laber, B., Pohlenz, HD., Messerschmidt, A. (1996)

Crystal structure of the pyridoxal-5'-phosphate dependent cystathionine beta-lyase from Escherichia coli at 1.83 A.

J Mol Biol. 262(2):202-24

1995

Stenberg, K., Clausen, T., Lindqvist, Y., Macheroux, P. (1995)

Involvement of Tyr24 and Trp108 in substrate binding and substrate specificity of glycolate oxidase.

Eur J Biochem. 228(2):408-16