Zweckstetter, Markus

[["dc.bibliographiccitation.firstpage","299"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Biomolecular NMR"],["dc.bibliographiccitation.lastpage","307"],["dc.bibliographiccitation.volume","63"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Narayanan, Raghavendran L."],["dc.contributor.author","Xiang, ShengQi"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T09:49:30Z"],["dc.date.available","2018-11-07T09:49:30Z"],["dc.date.issued","2015"],["dc.description.abstract","Intrinsically disordered proteins (IDPs) are best described by ensembles of conformations and a variety of approaches have been developed to determine IDP ensembles. Because of the large number of conformations, however, cross-validation of the determined ensembles by independent experimental data is crucial. The (1)J(C alpha H alpha) coupling constant is particularly suited for cross-validation, because it has a large magnitude and mostly depends on the often less accessible dihedral angle psi. Here, we reinvestigated the connection between (1)J(C alpha H alpha) values and protein backbone dihedral angles. We show that accurate amino-acid specific random coil values of the (1)J(C alpha H alpha) coupling constant, in combination with a reparameterized empirical Karplus-type equation, allow for reliable cross-validation of molecular ensembles of IDPs."],["dc.description.sponsorship","DFG [ZW71/8-1]"],["dc.identifier.doi","10.1007/s10858-015-9990-z"],["dc.identifier.isi","000365088800008"],["dc.identifier.pmid","26433382"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35521"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","1573-5001"],["dc.relation.issn","0925-2738"],["dc.title","Improved validation of IDP ensembles by one-bond C alpha-H alpha scalar couplings"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13010"],["dc.bibliographiccitation.issue","53"],["dc.bibliographiccitation.journal","Chemistry - A European Journal"],["dc.bibliographiccitation.lastpage","13014"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Fonseca-Ornelas, Luis"],["dc.contributor.author","Schmidt, Carla"],["dc.contributor.author","Camacho-Zarco, Aldo R."],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2020-12-10T14:05:47Z"],["dc.date.available","2020-12-10T14:05:47Z"],["dc.date.issued","2017"],["dc.identifier.doi","10.1002/chem.201703001"],["dc.identifier.issn","0947-6539"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/69658"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Small-Molecule-Induced Soluble Oligomers of α-Synuclein with Helical Structure"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Strohäker, Timo"],["dc.contributor.author","Jung, Byung Chul"],["dc.contributor.author","Liou, Shu-Hao"],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Halliday, Glenda M."],["dc.contributor.author","Bennati, Marina"],["dc.contributor.author","Kim, Woojin S."],["dc.contributor.author","Lee, Seung-Jae"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2020-12-10T18:09:52Z"],["dc.date.available","2020-12-10T18:09:52Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41467-019-13564-w"],["dc.identifier.eissn","2041-1723"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17027"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73784"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Structural heterogeneity of α-synuclein fibrils amplified from patient brain extracts"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","jacs.2c07149"],["dc.bibliographiccitation.journal","Journal of the American Chemical Society"],["dc.contributor.author","Babu, Maria"],["dc.contributor.author","Favretto, Filippo"],["dc.contributor.author","Rankovic, Marija"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2022-09-01T09:49:58Z"],["dc.date.available","2022-09-01T09:49:58Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1021/jacs.2c07149"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/113586"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-597"],["dc.relation.eissn","1520-5126"],["dc.relation.issn","0002-7863"],["dc.title","Peptidyl Prolyl Isomerase A Modulates the Liquid–Liquid Phase Separation of Proline-Rich IDPs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8685"],["dc.bibliographiccitation.issue","25"],["dc.bibliographiccitation.journal","Chemistry - A European Journal"],["dc.bibliographiccitation.lastpage","8693"],["dc.bibliographiccitation.volume","22"],["dc.contributor.author","Beyer, Isaak"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Klafki, Hans-Wolfgang"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Haußmann, Ute"],["dc.contributor.author","Wiltfang, Jens"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Knölker, Hans-Joachim"],["dc.date.accessioned","2017-09-07T11:44:41Z"],["dc.date.available","2017-09-07T11:44:41Z"],["dc.date.issued","2016"],["dc.description.abstract","In addition to the prototypic amyloid-β (Aβ) peptides Aβ1–40 and Aβ1–42, several Aβ variants differing in their amino and carboxy termini have been described. Synthetic availability of an Aβ variant is often the key to study its role under physiological or pathological conditions. Herein, we report a protocol for the efficient solid-phase peptide synthesis of the N-terminally elongated Aβ-peptides Aβ−3–38, Aβ−3–40, and Aβ−3–42. Biophysical characterization by NMR spectroscopy, CD spectroscopy, an aggregation assay, and electron microscopy revealed that all three peptides were prone to aggregation into amyloid fibrils. Immunoprecipitation, followed by mass spectrometry, indicated that Aβ−3–38 and Aβ−3–40 are generated by transfected cells even in the presence of a tripartite β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor. The elongated Aβ peptides starting at Val(−3) can be separated from N-terminally-truncated Aβ forms by high-resolution isoelectric-focusing techniques, despite virtually identical isoelectric points. The synthetic Aβ variants and the methods presented here are providing tools to advance our understanding of the potential roles of N-terminally elongated Aβ variants in Alzheimer's disease."],["dc.identifier.doi","10.1002/chem.201600892"],["dc.identifier.gro","3151723"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14030"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8544"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.issn","0947-6539"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Solid-Phase Synthesis and Characterization of N-Terminally Elongated Aβ−3-x-Peptides"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2162"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Structure"],["dc.bibliographiccitation.lastpage","2174"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","Xiang, Shengqi"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Kim, Hai-Young"],["dc.contributor.author","Bessonov, Sergey"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Moehlmann, Sina"],["dc.contributor.author","Klaukien, Volker"],["dc.contributor.author","Ficner, Ralf"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Luehrmann, Reinhard"],["dc.contributor.author","Groot, Bert L. de"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:46:59Z"],["dc.date.available","2017-09-07T11:46:59Z"],["dc.date.issued","2013"],["dc.description.abstract","Serine/arginine-rich (SR) proteins are important players in RNA metabolism and are extensively phosphorylated at serine residues in RS repeats. Here, we show that phosphorylation switches the RS domain of the serine/arginine-rich splicing factor 1 from a fully disordered state to a partially rigidified arch-like structure. Nuclear magnetic resonance spectroscopy in combination with molecular dynamics simulations revealed that the conformational switch is restricted to RS repeats, critically depends on the phosphate charge state and strongly decreases the conformational entropy of RS domains. The dynamic switch also occurs in the 100 kDa SR-related protein hPrp28, for which phosphorylation at the RS repeat is required for spliceosome assembly. Thus, a phosphorylation-induced dynamic switch is common to the class of serine/arginine-rich proteins and provides a molecular basis for the functional redundancy of serine/arginine-rich proteins and the profound influence of RS domain phosphorylation on protein-protein and protein-RNA interactions."],["dc.identifier.doi","10.1016/j.str.2013.09.014"],["dc.identifier.gro","3142236"],["dc.identifier.isi","000328914900010"],["dc.identifier.pmid","24183573"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6043"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1878-4186"],["dc.relation.issn","0969-2126"],["dc.title","Phosphorylation Drives a Dynamic Switch in Serine/Arginine-Rich Proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","109"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Annals of Neurology"],["dc.bibliographiccitation.lastpage","118"],["dc.bibliographiccitation.volume","74"],["dc.contributor.author","Taschenberger, G."],["dc.contributor.author","Toloe, J."],["dc.contributor.author","Tereshchenko, J."],["dc.contributor.author","Akerboom, J."],["dc.contributor.author","Wales, P."],["dc.contributor.author","Benz, R."],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Outeiro, T. F."],["dc.contributor.author","Looger, L. L."],["dc.contributor.author","Bähr, M."],["dc.contributor.author","Zweckstetter, M."],["dc.contributor.author","Kügler, Sebastian"],["dc.date.accessioned","2017-09-07T11:47:39Z"],["dc.date.available","2017-09-07T11:47:39Z"],["dc.date.issued","2013"],["dc.description.abstract","ObjectiveWhereas the contribution of -synuclein to neurodegeneration in Parkinson disease is well accepted, the putative impact of its close homologue, -synuclein, is enigmatic. -Synuclein is widely expressed throughout the central nervous system, as is -synuclein, but the physiological functions of both proteins remain unknown. Recent findings have supported the view that -synuclein can act as an ameliorating regulator of -synuclein-induced neurotoxicity, having neuroprotective rather than neurodegenerative capabilities, and being nonaggregating due to the absence of most of the aggregation-promoting NAC domain. However, a mutation of -synuclein linked to dementia with Lewy bodies rendered the protein neurotoxic in transgenic mice, and fibrillation of -synuclein has been demonstrated in vitro. MethodsNeurotoxicity and aggregation properties of -, -, and -synuclein were comparatively elucidated in the rat nigro-striatal projection and in cultured neurons. ResultsSupporting the hypothesis that -synuclein can act as a neurodegeneration-inducing factor, we demonstrated that wild-type -synuclein is neurotoxic for cultured primary neurons. Furthermore, -synuclein formed proteinase K-resistant aggregates in dopaminergic neurons in vivo, leading to pronounced and progressive neurodegeneration in rats. Expression of -synuclein caused mitochondrial fragmentation, but this fragmentation did not render mitochondria nonfunctional in terms of ion handling and respiration even at late stages of neurodegeneration. A comparison of the neurodegenerative effects induced by -, -, and -synuclein revealed that -synuclein was eventually as neurotoxic as -synuclein for nigral dopaminergic neurons, whereas -synuclein proved to be nontoxic and had very low aggregation propensity. InterpretationOur results suggest that the role of -synuclein as a putative modulator of neuropathology in aggregopathies like Parkinson disease and dementia with Lewy bodies needs to be revisited. Ann Neurol 2013;74:109-118"],["dc.identifier.doi","10.1002/ana.23905"],["dc.identifier.gro","3142329"],["dc.identifier.isi","000329198600014"],["dc.identifier.pmid","23536356"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7075"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1531-8249"],["dc.relation.issn","0364-5134"],["dc.title","β-Synuclein Aggregates and Induces Neurodegeneration in Dopaminergic Neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","5857"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Fonseca-Ornelas, Luis"],["dc.contributor.author","Eisbach, Sibylle E."],["dc.contributor.author","Paulat, Maria"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T09:31:47Z"],["dc.date.available","2018-11-07T09:31:47Z"],["dc.date.issued","2014"],["dc.description.abstract","alpha-synuclein is an abundant presynaptic protein that is important for regulation of synaptic vesicle trafficking, and whose misfolding plays a key role in Parkinson's disease. While alpha-synuclein is disordered in solution, it folds into a helical conformation when bound to synaptic vesicles. Stabilization of helical, folded alpha-synuclein might therefore interfere with alpha-synuclein-induced neurotoxicity. Here we show that several small molecules, which delay aggregation of alpha-synuclein in solution, including the Parkinson's disease drug selegiline, fail to interfere with misfolding of vesicle-bound alpha-synuclein. In contrast, the porphyrin phtalocyanine tetrasulfonate directly binds to vesicle-bound alpha-synuclein, stabilizes its helical conformation and thereby delays pathogenic misfolding and aggregation. Our study suggests that small-molecule-mediated stabilization of helical vesicle-bound alpha-synuclein opens new possibilities to target Parkinson's disease and related synucleinopathies."],["dc.identifier.doi","10.1038/ncomms6857"],["dc.identifier.isi","000347683000001"],["dc.identifier.pmid","25524885"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31609"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-1723"],["dc.title","Small molecule-mediated stabilization of vesicle-associated helical alpha-synuclein inhibits pathogenic misfolding and aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e2001336"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Baker, Jeremy D."],["dc.contributor.author","Shelton, Lindsey B."],["dc.contributor.author","Zheng, Dali"],["dc.contributor.author","Favretto, Filippo"],["dc.contributor.author","Nordhues, Bryce A."],["dc.contributor.author","Darling, April"],["dc.contributor.author","Sullivan, Leia E."],["dc.contributor.author","Sun, Zheying"],["dc.contributor.author","Solanki, Parth K."],["dc.contributor.author","Martin, Mackenzie D."],["dc.contributor.author","Suntharalingam, Amirthaa"],["dc.contributor.author","Sabbagh, Jonathan J."],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Mandelkow, Eckhard"],["dc.contributor.author","Uversky, Vladimir N."],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Dickey, Chad A."],["dc.contributor.author","Koren, John, III"],["dc.contributor.author","Blair, Laura J."],["dc.date.accessioned","2018-11-07T10:22:54Z"],["dc.date.available","2018-11-07T10:22:54Z"],["dc.date.issued","2017"],["dc.description.abstract","The accumulation of amyloidogenic proteins is a pathological hallmark of neurodegenerative disorders. The aberrant accumulation of the microtubule associating protein tau (MAPT, tau) into toxic oligomers and amyloid deposits is a primary pathology in tauopathies, the most common of which is Alzheimer's disease (AD). Intrinsically disordered proteins, like tau, are enriched with proline residues that regulate both secondary structure and aggregation propensity. The orientation of proline residues is regulated by cis/trans peptidyl-prolyl isomerases (PPIases). Here we show that cyclophilin 40 (CyP40), a PPIase, dissolves tau amyloids in vitro. Additionally, CyP40 ameliorated silver-positive and oligomeric tau species in a mouse model of tau accumulation, preserving neuronal health and cognition. Nuclear magnetic resonance (NMR) revealed that CyP40 interacts with tau at sites rich in proline residues. CyP40 was also able to interact with and disaggregate other aggregating proteins that contain prolines. Moreover, CyP40 lacking PPIase activity prevented its capacity for disaggregation in vitro. Finally, we describe a unique structural property of CyP40 that may permit disaggregation to occur in an energy-independent manner. This study identifies a novel human protein disaggregase and, for the first time, demonstrates its capacity to dissolve intracellular amyloids."],["dc.identifier.doi","10.1371/journal.pbio.2001336"],["dc.identifier.isi","000404510400007"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14553"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42356"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.issn","1545-7885"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Human cyclophilin 40 unravels neurotoxic amyloids"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","566"],["dc.bibliographiccitation.journal","Biochemical Society Transactions"],["dc.bibliographiccitation.lastpage","571"],["dc.bibliographiccitation.volume","43"],["dc.contributor.author","Jaremko, Mariusz"],["dc.contributor.author","Jaremko, Lukasz"],["dc.contributor.author","Jaipuria, Garima"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T09:53:51Z"],["dc.date.available","2018-11-07T09:53:51Z"],["dc.date.issued","2015"],["dc.description.abstract","The 3D structure of the 18-kDa transmembrane (TM) protein TSPO (translocator protein)/PBR (peripheral benzodiazepine receptor), which contains a binding site for benzodiazepines, is important to better understand its function and regulation by endogenous and synthetic ligands. We have recently determined the structure of mammalian TSPO/PBR in complex with the diagnostic ligand PK11195 [1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide; Jaremko et al. (2014) Science 343, 1363-1366], providing for the first time atomic-level insight into the conformation of this protein, which is up-regulated in various pathological conditions including Alzheimer's disease and Parkinson's disease. Here, we review the studies which have probed the structural properties of mammalian TSPO/PBR as well as the homologues bacterial tryptophan-rich sensory proteins (TspOs) over the years and provide detailed insight into the 3D structure of mouse TSPO (mTSPO)/PBR in complex with PK11195."],["dc.identifier.doi","10.1042/BST20150029"],["dc.identifier.isi","000359001400006"],["dc.identifier.pmid","26551694"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36416"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Portland Press Ltd"],["dc.relation.issn","1470-8752"],["dc.relation.issn","0300-5127"],["dc.title","Structure of the mammalian TSPO/PBR protein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]