SCHINDELIN Gruppe

"Die Form folgt der Funktion”, dieser Leitsatz der Architektur des 20. Jahrhunderts fasst folgende Idee zusammen: Die Architektur eines Gebäudes sollte seine geplante Funktion widerspiegeln. In der Strukturbiologie gilt dieses Prinzip in umgekehrter Form, da die Kenntnis der dreidimensionalen Struktur eines biologischen Makromoleküls entscheidend für das Verständnis seiner Funktion ist, d.h. hier „Folgt die Funktion aus der Form“. Dieser Leitsatz motiviert unsere Forschungen in denen wir vor allem auf die Kristallstrukturanalyse zurückgreifen, eine Technik, die es erlaubt, die Struktur sowohl löslicher als auch membranständiger Proteine bei hoher Auflösung aufzuklären. Daneben kommen aber auch komplementäre biochemische, biophysikalische und zellbiologische Experimente zum Einsatz.

Struktur und Funktion von Proteinen

Zwei Themenkomplexe bilden die Kernpunkte unserer Untersuchungen:

(1) Protein Faltung und Reifung im endoplasmatischen Retikulum sowie der Abbau von Proteinen durch das Ubiquitin-Proteasom-System.

(2) Signalübertragung  in Nervenzellen mittels inhibitorischer Glyzin und GABA(A) Rezeptoren und deren Verankerung und Transport in postsynaptischen Zellen.

all Publications

Kasaragod V.B., Pacios-Michelena A., Schaefer N., Zheng F., Bader N., Alzheimer C., Villmann C., Schindelin H. Pyridoxal kinase inhibition by artemisinins down-regulates inhibitory neurotransmission. Proc Natl Acad Sci U S A. 2020 Dec 29;117(52):33235-33245. doi: 10.1073/pnas.2008695117. Epub 2020 Dec 14.

Kim R.Q., Misra M., Gonzalez A., Tomašković I., Shin D., Schindelin H., Filippov D.V., Ovaa H., Đikić I., van der Heden van Noort G.J. Development of ADPribosyl Ubiquitin Analogues to Study Enzymes Involved in Legionella Infection. Chemistry. 2020 Oct 19. doi: 10.1002/chem.202004590.

Green J.L., Wu Y., Encheva V., Lasonder E., Prommaban A., Kunzelmann S., Christodoulou E., Grainger M., Truongvan N., Bothe S., Sharma V., Song W., Pinzuti I., Uthaipibull C., Srichairatanakool S., Birault V., Langsley G., Schindelin H., Stieglitz B., Snijders A.P., Holder A.A. Ubiquitin activation is essential for schizont maturation in Plasmodium falciparum blood-stage development. PLoS Pathog. 2020 Jun 22;16(6):e1008640. doi: 10.1371/journal.ppat.1008640.

Jeanclos E., Knobloch G., Hoffmann A., Fedorchenko O., Odersky A., Lamprecht A.K., Schindelin H., Gohla A. Ca2+ functions as a molecular switch that controls the mutually exclusive complex formation of pyridoxal phosphatase with CIB1 or calmodulin. FEBS Lett. 2020 Apr 23. doi: 10.1002/1873-3468.13795.

Dietschreit J.C.B., Wagner A., Le T.A., Klein P., Schindelin H., Opatz T., Engels B., Hellmich U.A., Ochsenfeld C. Predicting 19 F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase-Inhibitor Complex. Angew Chem Int Ed Engl. 2020 Jul 27;59(31):12669-12673. doi: 10.1002/anie.202000539. Epub 2020 May 25.

Mostosi P., Schindelin H., Kollmannsberger P., Thorn A. Haruspex: A Neural Network for the Automatic Identification of Oligonucleotides and Protein Secondary Structure in Cryo-Electron Microscopy Maps. Angew Chem Int Ed Engl. 2020 Mar 18;59(35):14788-95. doi: 10.1002/anie.202000421.

Hänzelmann P., Galgenmüller C., Schindelin H. Structure and Function of the AAA+ ATPase p97, a Key Player in Protein Homeostasis.  Subcell Biochem. 2019;93:221-272. doi: 10.1007/978-3-030-28151-9_7.

Sereikaite V., Fritzius T., Kasaragod V.B., Bader N., Maric H.M., Schindelin H., Bettler B., Strømgaard K. Targeting the γ-Aminobutyric Acid Type B (GABAB) Receptor Complex: Development of Inhibitors Targeting the K+ Channel Tetramerization Domain (KCTD) Containing Proteins/GABAB Receptor Protein-Protein Interaction. J Med Chem. 2019 Oct 10;62(19):8819-8830. doi: 10.1021/acs.jmedchem.9b01087. Epub 2019 Sep 25.

Kasaragod V.B., Schindelin H. Structure of Heteropentameric GABAA Receptors and Receptor-Anchoring Properties of Gephyrin. Front Mol Neurosci. 2019 Aug 7;12:191. doi: 10.3389/fnmol.2019.00191.

Kitzenmaier A., Schaefer N., Kasaragod V.B., Polster T., Hantschmann R., Schindelin H., Villmann C. The P429L loss of function mutation of the human glycine transporter 2 associated with hyperekplexia. Eur J Neurosci. 2019 Dec;50(12):3906-3920. doi: 10.1111/ejn.14533. Epub 2019 Sep 5.

Viet K.K., Wagner A., Schwickert K., Hellwig N., Brennich M., Bader N., Schirmeister T., Morgner N., Schindelin H., Hellmich U.A. Structure of the Human TRPML2 Ion Channel Extracytosolic/Lumenal Domain. Structure. 2019 Aug 6;27(8):1246-1257.e5. doi: 10.1016/j.str.2019.04.016. Epub 2019 Jun 6.

Bansal A., Karanth N.M., Demeler B., Schindelin H., Sarma S.P. Crystallographic Structures of IlvN·Val/Ile Complexes: Conformational Selectivity for Feedback Inhibition of Aceto Hydroxy Acid Synthases. Biochemistry. 2019 Apr 16;58(15):1992-2008. doi: 10.1021/acs.biochem.9b00050. Epub 2019 Mar 29.

Kasaragod V, Hausrat TJ, Schaefer N, Kuhn M, Christensen NR, Tessmer I, Maric HM, Lindegaard Madsen K, Sotriffer C, Villmann C, Kneussel M, Schindelin H. Elucidating the Molecular Basis for Inhibitory Neurotransmission Regulation by Artemisinins. Neuron 2019 Jan 28 doi:doi.org/10.1016/j.neuron.2019.01.001. [Epub ahead of print]

Wagner A, Le TA, Brennich M, Klein P, Bader N, Diehl E, Paszek D, Weickhmann AK, Dirdjaja N, Krauth-Siegel RL, Engels B, Opatz T, Schindelin H, Hellmich UA. Inhibitor-induced dimerization of an essential oxidoreductase from African Trypanosomes. Angew Chem Int Ed Engl. 2019 Jan 3. doi: 10.1002/anie.201810470. [Epub ahead of print]

Hines RM, Maric HM, Hines DJ, Modgil A, Panzanelli P, Nakamura Y, Nathanson AJ, Cross A, Deeb T, Brandon NJ, Davies P, Fritschy JM, Schindelin H, Moss SJ. Developmental seizures and mortality result from reducing GABAA receptor α2-subunit interaction with collybistin. Nat Commun. 2018 Aug 7;9(1):3130. doi: 10.1038/s41467-018-05481-1.

Misra M., Kuhn M., Löbel M., An H., Statsyuk A.V., Sotriffer C., Schindelin H. (2017). Dissecting the Specificity of Adenosyl Sulfamate Inhibitors Targeting the Ubiquitin-Activating Enzyme. Structure. 2017 Jul 5;25(7):1120-1129.e3. doi: 10.1016/j.str.2017.05.001. Epub 2017 Jun 1.

Kasaragod, V.B., Schindelin, H. (2016). Structural Framework for Metal Incorporation during Molybdenum Cofactor Biosynthesis. Structure. May 3;24(5):782-8. doi: 10.1016/j.str.2016.02.023. Epub Apr 21.

Hänzelmann, P.; Schindelin, H. (2016). Characterization of an Additional Binding Surface on the p97 N-Terminal Domain Involved in Bipartite Cofactor Interactions. Structure. 24(1): 140-7. doi: 10.1016/j.str.2015.10.026. Epub 2015 Dec 17.

Hänzelmann, P.; Schindelin, H. (2016). Structural Basis of ATP Hydrolysis and Intersubunit Signaling in the AAA+ ATPase p97. Structure. 24(1):127-39. doi: 10.1016/j.str.2015.10.026. Epub 2015 Dec 17.

Delto C.F., Heisler F.F., Kuper J., Sander B., Kneussel M., Schindelin H. (2015). The LisH motif of muskelin is crucial for oligomerization and governs intracellular localization. Structure. 2015 Feb 3;23(2):364-73. doi: 10.1016/j.str.2014.11.016. Epub 2015 Jan 8.

Maric H.M., Kasaragod V.B., Hausrat T.J., Kneussel M., Tretter V., Strømgaard K., Schindelin H. (2014). Molecular basis of the alternative recruitment of GABA(A) versus glycine receptors through gephyrin. Nat Commun. 2014 Dec 22;5:5767. doi: 10.1038/ncomms6767.

Maric H.M., Kasaragod V.B., Haugaard-Kedström L., Hausrat T.J., Kneussel M., Schindelin H., Strømgaard K. (2015). Design and synthesis of high-affinity dimeric inhibitors targeting the interactions between gephyrin and inhibitory neurotransmitter receptors. Angew Chem Int Ed Engl. 2015 Jan 7;54(2):490-4. doi: 10.1002/anie.201409043. Epub 2014 Nov 20.

Soykan T., Schneeberger D., Tria G., Buechner C., Bader N., Svergun D., Tessmer I, Poulopoulos A, Papadopoulos T, Varoqueaux F, Schindelin H, Brose N. (2014). A conformational switch in collybistin determines the differentiation of inhibitory postsynapses. EMBO J. 2014 Sep 17;33(18):2113-33. doi: 10.15252/embj.201488143. Epub 2014 Jul 30.

Grimm C., Chari A., Pelz J.P., Kuper J., Kisker C., Diederichs K., Stark H., Schindelin H., Fischer U. (2013). Structural basis of assembly chaperone- mediated snRNP formation. Mol Cell. 2013 Feb 21;49(4):692-703. doi: 10.1016/j.molcel.2012.12.009. Epub 2013 Jan 17.

Maric H.M., Mukherjee J., Tretter V., Moss S.J., Schindelin H. (2011). Gephyrin-mediated γ-aminobutyric acid type A and glycine receptor clustering relies on a common binding site. J Biol Chem. 2011 Dec 9;286(49):42105-14. doi: 10.1074/jbc.M111.303412. Epub 2011 Oct 17.

Hänzelmann P., Schindelin H. (2011). The structural and functional basis of the p97/valosin-containing protein (VCP)-interacting motif (VIM): mutually exclusive binding of cofactors to the N-terminal domain of p97. J Biol Chem. 2011 Nov 4;286(44):38679-90. doi: 10.1074/jbc.M111.274506. Epub 2011 Sep 13.

Hänzelmann P., Buchberger A., Schindelin H. (2011). Hierarchical binding of cofactors to the AAA ATPase p97. Structure. 2011 Jun 8;19(6):833-43. doi: 10.1016/j.str.2011.03.018.

Lee I., Schindelin H. (2008). Structural insights into E1-catalyzed ubiquitin activation and transfer to conjugating enzymes. Cell. 2008 Jul 25;134(2):268-78. doi: 10.1016/j.cell.2008.05.046.

Kim E.Y., Schrader N., Smolinsky B., Bedet C., Vannier C., Schwarz G., Schindelin H. Deciphering the structural framework of glycine receptor anchoring by gephyrin. EMBO J. 2006 Mar 22;25(6):1385-95. Epub 2006 Mar 2.

Tian G., Xiang S., Noiva R., Lennarz W.J., Schindelin H. (2006). The crystal structure of yeast protein disulfide isomerase suggests cooperativity between its active sites. Cell. 2006 Jan 13;124(1):61-73. Erratum in: Cell. 2006 Mar 10;124(5):1085-8.

Hänzelmann P., Schindelin H. (2004). Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans. Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12870-5. Epub 2004 Aug 18.

Lake M.W., Leimkühler S., Wuebbens M.M., Rajagopalan K.V., H. Schindelin. (2001). “The crystal structure of the MoeB-MoaD complex provides insights into the mechanism of ubiquitin activation”, Nature 414, 325-329.

Rudolph M.J., Wuebbens M.M., Rajagopalan K.V., Schindelin H. (2001). Crystal structure of molybdopterin synthase and its evolutionary relationship to ubiquitin-activation. Nature Struct. Biol. 8, 42-46.

Current position

Professor of Structural Biology and Biochemistry at the Rudolf Virchow Center of  University of Würzburg (since 2006)

Research Experience

2002-2006   Associate Professor, Stony Brook University, USA
1998-2002   Assistant Professor, Stony Brook University, USA
1994-1998   Postdoc, California Institute of Technology, Pasadena, CA, USA

Education

1991-1994    Dr. rer. nat (PhD) Biochemistry and Structural Biology, Freie Universität Berlin, Germany

Awards and Fellowships

• Graduate Fellowship Deutsche Forschungsgemeinschaft (1991-1994)
• Postdoctoral Fellowship from the Deutsche Forschungsgemeinschaft (1995-1997)
• Postdoctoral Fellowship from the Howard Hughes Medical Institute (1997-1998)
• Targeted Research Opportunity Award, Stony Brook University (2001-2003)

Selected professional activities

• Member of Participating Research Team of Beam Line X26C at the National Synchrotron Light Source at Brookhaven National Laboratory (1998-2006)
• Spokesperson for the Participating Research Team of Beam Line X26C at the National Synchrotron Light Source at Brookhaven National Laboratory (2004-2006)
• Member of the Admissions Committee for the Graduate Program in Molecular and Cellular Biology (2000-2001)
• Director of Admissions for Graduate Program in Biochemistry and Structural Biology (2000-2006) 
• Member of the Molecular and Cellular Biology Graduate Program Executive Committee (2000-2006)
• Speaker of the section Molecular Biosciences within the Graduate School of Life Sciences at the Uni Würzburg (since 2014)
• Speaker Interest Group 1 “Biological Crstallography” of the German Society for Crystallography (since 2014)
• Coopted member of the “Committee on Research with Synchrotron Radiation” (since 2015)
• Member of the Editorial Board of the Journal of Biological Chemistry (since 2015)

Position

Professor für Biochemie/Strukturbiologie - Rudolf-Virchow-Zentrum
Mitglied - Graduate School of Life Sciences
Supervisor und Mitglied in verschiedenen Promotionskomitees - Graduate School of Life Sciences/Biomedizin 

Lehrveranstaltungen

• Struktur und Funktion biologischer Makromoleküle (für Bachelorstudenten)
• Makromolekulare Kristallographie (für Masterstudenten)
• Literaturseminar Ubiquitin- Proteasom- System (für Masterstudenten und Doktoranden)
• Literaturseminar Inonenkanäle und assoziierte Proteine (für Masterstudenten und Doktoranden)
• Studienbegleitende Mitarbeit im Forschungslabor (für Bachelor- und Masterstudenten)

Weiter Infos zu den Lehrveranstaltungen finden Sie hier.