Dr. Jana Sticht
Studying MHC proteins with NMR Spectroscopy.
Biochemistry
Staff Scientists - NMR Facility
Protein Biochemistry
14195 Berlin
As a staff scientist and member of the NMR facility Jana Sticht supports the group in protein NMR spectroscopy applications. This comprises standard approaches for protein backbone assignments and protein-ligand interactions, as well as applications tailored towards the investigation of intrinsically disordered proteins and protein dynamics. In the Freund group, NMR spectroscopy has for example been used in projects investigating the proteins ADAP (involved in T cell function), FBP21 (part of the spliceosomal B-complex), and proteins involved in SNARE complex formation. Predominantly, Jana Sticht has been involved in many projects unravelling the mechanistic details of MHC antigen presentation.
Jana Sticht studied biochemistry at the FU Berlin gaining an interest in projects targeting biomedical topics. For her PhD in structural virology she went to the group of Prof. Kräusslich at the University of Heidelberg to work on “HIV-1 capsid assembly and its inhibition”. Jana joined the Freund group as PostDoc in 2005 to work on the mechanism of MHC class II peptide presentation using NMR spectroscopy. Since 2016 she supports protein NMR spectroscopy projects in the department as a member of the Core Facility BioSupraMol. Besides that she continues to work on MHC antigen presentation in the Freund group.
1: Günther M, Sticht J, Freund C, Höfer T. Antigen presentation by MHC-II is shaped by competitive and cooperative allosteric mechanisms of peptide exchange. Structure. 2025 Feb 6;33(2):389-400.e13. doi: 10.1016/j.str.2024.11.014.
2: Abualrous ET, Stolzenberg S, Sticht J, Wieczorek M, Roske Y, Günther M, Dähn S, Boesen BB, Calvo MM, Biese C, Kuppler F, Medina-García Á, Álvaro-Benito M, Höfer T, Noé F, Freund C. MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange. Nat Chem Biol. 2023 Oct;19(10):1196-1204. doi: 10.1038/s41589-023-01316-3.
3: Jia Y, Schroeder B, Pfeifer Y, Fröhlich C, Deng L, Arkona C, Kuropka B, Sticht J, Ataka K, Bergemann S, Wolber G, Nitsche C, Mielke M, Leiros HS, Werner G, Rademann J. Kinetics, Thermodynamics, and Structural Effects of Quinoline-2-Carboxylates, Zinc-Binding Inhibitors of New Delhi Metallo-β-lactamase-1 Re-sensitizing Multidrug-Resistant Bacteria for Carbapenems. J Med Chem. 2023 Sep 14;66(17):11761-11791. doi: 10.1021/acs.jmedchem.3c00171.
4: Wenz MT, Bertazzon M, Sticht J, Aleksić S, Gjorgjevikj D, Freund C, Keller BG. Target Recognition in Tandem WW Domains: Complex Structures for Parallel and Antiparallel Ligand Orientation in h-FBP21 Tandem WW. J Chem Inf Model. 2022 Dec 26;62(24):6586-6601. doi: 10.1021/acs.jcim.1c01426.
5: Lan H, Abualrous ET, Sticht J, Fernandez LMA, Werk T, Weise C, Ballaschk M, Schmieder P, Loll B, Freund C. Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules. Nat Commun. 2021 Jul 9;12(1):4236. doi: 10.1038/s41467-021-24401-4.
6: Sticht J, Álvaro-Benito M, Konigorski S. Type 1 Diabetes and the HLA Region: Genetic Association Besides Classical HLA Class II Genes. Front Genet. 2021 Jun 17;12:683946. doi: 10.3389/fgene.2021.683946.
7: Abualrous ET, Sticht J, Freund C. Major histocompatibility complex (MHC) class I and class II proteins: impact of polymorphism on antigen presentation. Curr Opin Immunol. 2021 Jun;70:95-104. doi: 10.1016/j.coi.2021.04.009.
8: Legrand C, Saleppico R, Sticht J, Lolicato F, Müller HM, Wegehingel S, Dimou E, Steringer JP, Ewers H, Vattulainen I, Freund C, Nickel W. The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P<sub>2</sub> facilitating unconventional secretion of Fibroblast Growth Factor 2. Commun Biol. 2020 Mar 25;3(1):141.
9: Gerth F, Jäpel M, Sticht J, Kuropka B, Schmitt XJ, Driller JH, Loll B, Wahl MC, Pagel K, Haucke V, Freund C. Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain. Structure. 2019 Jun 4;27(6):977-987.e5. doi: 10.1016/j.str.2019.03.020.
10: Sticht J, Bertazzon M, Henning LM, Licha JR, Abualrous ET, Freund C. FBP21's C-Terminal Domain Remains Dynamic When Wrapped around the c-Sec63 Unit of Brr2 Helicase. Biophys J. 2019 Feb 5;116(3):406-418. doi: 10.1016/j.bpj.2018.11.3123.
11: Wollenhaupt J, Henning LM, Sticht J, Becke C, Freund C, Santos KF, Wahl MC. Intrinsically Disordered Protein Ntr2 Modulates the Spliceosomal RNA Helicase Brr2. Biophys J. 2018 Feb 27;114(4):788-799. doi: 10.1016/j.bpj.2017.12.033.
12: Henning LM, Santos KF, Sticht J, Jehle S, Lee CT, Wittwer M, Urlaub H, Stelzl U, Wahl MC, Freund C. A new role for FBP21 as regulator of Brr2 helicase activity. Nucleic Acids Res. 2017 Jul 27;45(13):7922-7937. doi: 10.1093/nar/gkx535.
13: Van Elssen CHMJ, Rashidian M, Vrbanac V, Wucherpfennig KW, Habre ZE, Sticht J, Freund C, Jacobsen JT, Cragnolini J, Ingram J, Plaisier L, Spierings E, Tager AM, Ploegh HL. Noninvasive Imaging of Human Immune Responses in a Human Xenograft Model of Graft-Versus-Host Disease. J Nucl Med. 2017 Jun;58(6):1003-1008. doi: 10.2967/jnumed.116.186007.
14: Witte A, Meineke B, Sticht J, Philipsen L, Kuropka B, Müller AJ, Freund C, Schraven B, Kliche S. D120 and K152 within the PH Domain of T Cell Adapter SKAP55 Regulate Plasma Membrane Targeting of SKAP55 and LFA-1 Affinity Modulation in Human T Lymphocytes. Mol Cell Biol. 2017 Mar 17;37(7):e00509-16. doi: 10.1128/MCB.00509-16.
15: Wieczorek M, Abualrous ET, Sticht J, Álvaro-Benito M, Stolzenberg S, Noé F, Freund C. Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation. Front Immunol. 2017 Mar 17;8:292. doi: 10.3389/fimmu.2017.00292.
16: Wieczorek M, Sticht J, Stolzenberg S, Günther S, Wehmeyer C, El Habre Z, Álvaro-Benito M, Noé F, Freund C. MHC class II complexes sample intermediate states along the peptide exchange pathway. Nat Commun. 2016 Nov 9;7:13224. doi: 10.1038/ncomms13224.
17: Alvaro-Benito M, Morrison E, Wieczorek M, Sticht J, Freund C. Human leukocyte Antigen-DM polymorphisms in autoimmune diseases. Open Biol. 2016 Aug;6(8):160165. doi: 10.1098/rsob.160165.
18: Kuropka B, Witte A, Sticht J, Waldt N, Majkut P, Hackenberger CP, Schraven B, Krause E, Kliche S, Freund C. Analysis of Phosphorylation-dependent Protein Interactions of Adhesion and Degranulation Promoting Adaptor Protein (ADAP) Reveals Novel Interaction Partners Required for Chemokine-directed T cell Migration. Mol Cell Proteomics. 2015 Nov;14(11):2961-72. doi: 10.1074/mcp.M115.048249.
19: Álvaro-Benito M, Wieczorek M, Sticht J, Kipar C, Freund C. HLA-DMA polymorphisms differentially affect MHC class II peptide loading. J Immunol. 2015 Jan 15;194(2):803-16. doi: 10.4049/jimmunol.1401389.
20: Yin L, Trenh P, Guce A, Wieczorek M, Lange S, Sticht J, Jiang W, Bylsma M, Mellins ED, Freund C, Stern LJ. Susceptibility to HLA-DM protein is determined by a dynamic conformation of major histocompatibility complex class II molecule bound with peptide. J Biol Chem. 2014 Aug 22;289(34):23449-64. doi: 10.1074/jbc.M114.585539.
21: Schlundt A, Günther S, Sticht J, Wieczorek M, Roske Y, Heinemann U, Freund C. Peptide linkage to the α-subunit of MHCII creates a stably inverted antigen presentation complex. J Mol Biol. 2012 Oct 26;423(3):294-302. doi: 10.1016/j.jmb.2012.07.008.
22: Günther S, Schlundt A, Sticht J, Roske Y, Heinemann U, Wiesmüller KH, Jung G, Falk K, Rötzschke O, Freund C. Bidirectional binding of invariant chain peptides to an MHC class II molecule. Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22219-24. doi: 10.1073/pnas.1014708107.
23: Schlundt A, Sticht J, Piotukh K, Kosslick D, Jahnke N, Keller S, Schuemann M, Krause E, Freund C. Proline-rich sequence recognition: II. Proteomics analysis of Tsg101 ubiquitin-E2-like variant (UEV) interactions. Mol Cell Proteomics. 2009 Nov;8(11):2474-86. doi: 10.1074/mcp.M800337-MCP200.
24: Schlundt A, Kilian W, Beyermann M, Sticht J, Günther S, Höpner S, Falk K, Roetzschke O, Mitschang L, Freund C. A xenon-129 biosensor for monitoring MHC-peptide interactions. Angew Chem Int Ed Engl. 2009;48(23):4142-5. doi:10.1002/anie.200806149. PMID: 19408266.
1: Günther M, Sticht J, Freund C, Höfer T. Antigen presentation by MHC-II is shaped by competitive and cooperative allosteric mechanisms of peptide exchange. Structure. 2025 Feb 6;33(2):389-400.e13. doi: 10.1016/j.str.2024.11.014.
2: Abualrous ET, Stolzenberg S, Sticht J, Wieczorek M, Roske Y, Günther M, Dähn S, Boesen BB, Calvo MM, Biese C, Kuppler F, Medina-García Á, Álvaro-Benito M, Höfer T, Noé F, Freund C. MHC-II dynamics are maintained in HLA-DR allotypes to ensure catalyzed peptide exchange. Nat Chem Biol. 2023 Oct;19(10):1196-1204. doi: 10.1038/s41589-023-01316-3.
3: Jia Y, Schroeder B, Pfeifer Y, Fröhlich C, Deng L, Arkona C, Kuropka B, Sticht J, Ataka K, Bergemann S, Wolber G, Nitsche C, Mielke M, Leiros HS, Werner G, Rademann J. Kinetics, Thermodynamics, and Structural Effects of Quinoline-2-Carboxylates, Zinc-Binding Inhibitors of New Delhi Metallo-β-lactamase-1 Re-sensitizing Multidrug-Resistant Bacteria for Carbapenems. J Med Chem. 2023 Sep 14;66(17):11761-11791. doi: 10.1021/acs.jmedchem.3c00171.
4: Wenz MT, Bertazzon M, Sticht J, Aleksić S, Gjorgjevikj D, Freund C, Keller BG. Target Recognition in Tandem WW Domains: Complex Structures for Parallel and Antiparallel Ligand Orientation in h-FBP21 Tandem WW. J Chem Inf Model. 2022 Dec 26;62(24):6586-6601. doi: 10.1021/acs.jcim.1c01426.
5: Lan H, Abualrous ET, Sticht J, Fernandez LMA, Werk T, Weise C, Ballaschk M, Schmieder P, Loll B, Freund C. Exchange catalysis by tapasin exploits conserved and allele-specific features of MHC-I molecules. Nat Commun. 2021 Jul 9;12(1):4236. doi: 10.1038/s41467-021-24401-4.
6: Sticht J, Álvaro-Benito M, Konigorski S. Type 1 Diabetes and the HLA Region: Genetic Association Besides Classical HLA Class II Genes. Front Genet. 2021 Jun 17;12:683946. doi: 10.3389/fgene.2021.683946.
7: Abualrous ET, Sticht J, Freund C. Major histocompatibility complex (MHC) class I and class II proteins: impact of polymorphism on antigen presentation. Curr Opin Immunol. 2021 Jun;70:95-104. doi: 10.1016/j.coi.2021.04.009.
8: Legrand C, Saleppico R, Sticht J, Lolicato F, Müller HM, Wegehingel S, Dimou E, Steringer JP, Ewers H, Vattulainen I, Freund C, Nickel W. The Na,K-ATPase acts upstream of phosphoinositide PI(4,5)P<sub>2</sub> facilitating unconventional secretion of Fibroblast Growth Factor 2. Commun Biol. 2020 Mar 25;3(1):141.
9: Gerth F, Jäpel M, Sticht J, Kuropka B, Schmitt XJ, Driller JH, Loll B, Wahl MC, Pagel K, Haucke V, Freund C. Exon Inclusion Modulates Conformational Plasticity and Autoinhibition of the Intersectin 1 SH3A Domain. Structure. 2019 Jun 4;27(6):977-987.e5. doi: 10.1016/j.str.2019.03.020.
10: Sticht J, Bertazzon M, Henning LM, Licha JR, Abualrous ET, Freund C. FBP21's C-Terminal Domain Remains Dynamic When Wrapped around the c-Sec63 Unit of Brr2 Helicase. Biophys J. 2019 Feb 5;116(3):406-418. doi: 10.1016/j.bpj.2018.11.3123.
11: Wollenhaupt J, Henning LM, Sticht J, Becke C, Freund C, Santos KF, Wahl MC. Intrinsically Disordered Protein Ntr2 Modulates the Spliceosomal RNA Helicase Brr2. Biophys J. 2018 Feb 27;114(4):788-799. doi: 10.1016/j.bpj.2017.12.033.
12: Henning LM, Santos KF, Sticht J, Jehle S, Lee CT, Wittwer M, Urlaub H, Stelzl U, Wahl MC, Freund C. A new role for FBP21 as regulator of Brr2 helicase activity. Nucleic Acids Res. 2017 Jul 27;45(13):7922-7937. doi: 10.1093/nar/gkx535.
13: Van Elssen CHMJ, Rashidian M, Vrbanac V, Wucherpfennig KW, Habre ZE, Sticht J, Freund C, Jacobsen JT, Cragnolini J, Ingram J, Plaisier L, Spierings E, Tager AM, Ploegh HL. Noninvasive Imaging of Human Immune Responses in a Human Xenograft Model of Graft-Versus-Host Disease. J Nucl Med. 2017 Jun;58(6):1003-1008. doi: 10.2967/jnumed.116.186007.
14: Witte A, Meineke B, Sticht J, Philipsen L, Kuropka B, Müller AJ, Freund C, Schraven B, Kliche S. D120 and K152 within the PH Domain of T Cell Adapter SKAP55 Regulate Plasma Membrane Targeting of SKAP55 and LFA-1 Affinity Modulation in Human T Lymphocytes. Mol Cell Biol. 2017 Mar 17;37(7):e00509-16. doi: 10.1128/MCB.00509-16.
15: Wieczorek M, Abualrous ET, Sticht J, Álvaro-Benito M, Stolzenberg S, Noé F, Freund C. Major Histocompatibility Complex (MHC) Class I and MHC Class II Proteins: Conformational Plasticity in Antigen Presentation. Front Immunol. 2017 Mar 17;8:292. doi: 10.3389/fimmu.2017.00292.
16: Wieczorek M, Sticht J, Stolzenberg S, Günther S, Wehmeyer C, El Habre Z, Álvaro-Benito M, Noé F, Freund C. MHC class II complexes sample intermediate states along the peptide exchange pathway. Nat Commun. 2016 Nov 9;7:13224. doi: 10.1038/ncomms13224.
17: Alvaro-Benito M, Morrison E, Wieczorek M, Sticht J, Freund C. Human leukocyte Antigen-DM polymorphisms in autoimmune diseases. Open Biol. 2016 Aug;6(8):160165. doi: 10.1098/rsob.160165.
18: Kuropka B, Witte A, Sticht J, Waldt N, Majkut P, Hackenberger CP, Schraven B, Krause E, Kliche S, Freund C. Analysis of Phosphorylation-dependent Protein Interactions of Adhesion and Degranulation Promoting Adaptor Protein (ADAP) Reveals Novel Interaction Partners Required for Chemokine-directed T cell Migration. Mol Cell Proteomics. 2015 Nov;14(11):2961-72. doi: 10.1074/mcp.M115.048249.
19: Álvaro-Benito M, Wieczorek M, Sticht J, Kipar C, Freund C. HLA-DMA polymorphisms differentially affect MHC class II peptide loading. J Immunol. 2015 Jan 15;194(2):803-16. doi: 10.4049/jimmunol.1401389.
20: Yin L, Trenh P, Guce A, Wieczorek M, Lange S, Sticht J, Jiang W, Bylsma M, Mellins ED, Freund C, Stern LJ. Susceptibility to HLA-DM protein is determined by a dynamic conformation of major histocompatibility complex class II molecule bound with peptide. J Biol Chem. 2014 Aug 22;289(34):23449-64. doi: 10.1074/jbc.M114.585539.
21: Schlundt A, Günther S, Sticht J, Wieczorek M, Roske Y, Heinemann U, Freund C. Peptide linkage to the α-subunit of MHCII creates a stably inverted antigen presentation complex. J Mol Biol. 2012 Oct 26;423(3):294-302. doi: 10.1016/j.jmb.2012.07.008.
22: Günther S, Schlundt A, Sticht J, Roske Y, Heinemann U, Wiesmüller KH, Jung G, Falk K, Rötzschke O, Freund C. Bidirectional binding of invariant chain peptides to an MHC class II molecule. Proc Natl Acad Sci U S A. 2010 Dec 21;107(51):22219-24. doi: 10.1073/pnas.1014708107.
23: Schlundt A, Sticht J, Piotukh K, Kosslick D, Jahnke N, Keller S, Schuemann M, Krause E, Freund C. Proline-rich sequence recognition: II. Proteomics analysis of Tsg101 ubiquitin-E2-like variant (UEV) interactions. Mol Cell Proteomics. 2009 Nov;8(11):2474-86. doi: 10.1074/mcp.M800337-MCP200.
24: Schlundt A, Kilian W, Beyermann M, Sticht J, Günther S, Höpner S, Falk K, Roetzschke O, Mitschang L, Freund C. A xenon-129 biosensor for monitoring MHC-peptide interactions. Angew Chem Int Ed Engl. 2009;48(23):4142-5. doi:10.1002/anie.200806149. PMID: 19408266.
25: Bartonova V, Igonet S, Sticht J, Glass B, Habermann A, Vaney MC, Sehr P, Lewis J, Rey FA, Kraüsslich HG. Residues in the HIV-1 capsid assembly inhibitor binding site are essential for maintaining the assembly-competent quaternary structure of the capsid protein. J Biol Chem. 2008 Nov 14;283(46):32024-33. doi: 10.1074/jbc.M804230200.
26: Sticht J, Humbert M, Findlow S, Bodem J, Müller B, Dietrich U, Werner J, Kräusslich HG. A peptide inhibitor of HIV-1 assembly in vitro. Nat Struct Mol Biol. 2005 Aug;12(8):671-7. doi: 10.1038/nsmb964.
27: Ternois F, Sticht J, Duquerroy S, Kräusslich HG, Rey FA. The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor. Nat Struct Mol Biol. 2005 Aug;12(8):678-82. doi: 10.1038/nsmb967.
25: Bartonova V, Igonet S, Sticht J, Glass B, Habermann A, Vaney MC, Sehr P, Lewis J, Rey FA, Kraüsslich HG. Residues in the HIV-1 capsid assembly inhibitor binding site are essential for maintaining the assembly-competent quaternary structure of the capsid protein. J Biol Chem. 2008 Nov 14;283(46):32024-33. doi: 10.1074/jbc.M804230200.
26: Sticht J, Humbert M, Findlow S, Bodem J, Müller B, Dietrich U, Werner J, Kräusslich HG. A peptide inhibitor of HIV-1 assembly in vitro. Nat Struct Mol Biol. 2005 Aug;12(8):671-7. doi: 10.1038/nsmb964.
27: Ternois F, Sticht J, Duquerroy S, Kräusslich HG, Rey FA. The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor. Nat Struct Mol Biol. 2005 Aug;12(8):678-82. doi: 10.1038/nsmb967.