Paulat, Maria

[["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.firstpage","2639"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Journal of the American Chemical Society"],["dc.bibliographiccitation.lastpage","2646"],["dc.bibliographiccitation.volume","139"],["dc.contributor.author","Xiang, Shengqi"],["dc.contributor.author","Kulminskaya, Natalia"],["dc.contributor.author","Habenstein, Birgit"],["dc.contributor.author","Biernat, Jacek"],["dc.contributor.author","Tepper, Katharina"],["dc.contributor.author","Paulat, Maria"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Lange, Adam"],["dc.contributor.author","Mandelkow, Eckhard"],["dc.contributor.author","Linser, Rasmus"],["dc.date.accessioned","2018-01-17T11:35:58Z"],["dc.date.available","2018-01-17T11:35:58Z"],["dc.date.issued","2017"],["dc.description.abstract","Fibrillar aggregates of Aβ and Tau in the brain are the major hallmarks of Alzheimer's disease. Most Tau fibers have a twisted appearance, but the twist can be variable and even absent. This ambiguity, which has also been associated with different phenotypes of tauopathies, has led to controversial assumptions about fibril constitution, and it is unclear to-date what the molecular causes of this polymorphism are. To tackle this question, we used solid-state NMR strategies providing assignments of non-seeded three-repeat-domain Tau3RD with an inherent heterogeneity. This is in contrast to the general approach to characterize the most homogeneous preparations by construct truncation or intricate seeding protocols. Here, carbon and nitrogen chemical-shift conservation between fibrils revealed invariable secondary-structure properties, however, with inter-monomer interactions variable among samples. Residues with variable amide shifts are localized mostly to N- and C-terminal regions within the rigid beta structure in the repeat region of Tau3RD. By contrast, the hexapeptide motif in repeat R3, a crucial motif for fibril formation, shows strikingly low variability of all NMR parameters: Starting as a nucleation site for monomer-monomer contacts, this six-residue sequence element also turns into a well-defined structural element upon fibril formation. Given the absence of external causes in vitro, the interplay of structurally differently conserved elements in this protein likely reflects an intrinsic property of Tau fibrils."],["dc.identifier.doi","10.1021/jacs.6b09619"],["dc.identifier.pmid","28124562"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11683"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1520-5126"],["dc.title","A Two-Component Adhesive: Tau Fibrils Arise from a Combination of a Well-Defined Motif and Conformationally Flexible Interactions"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3269"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","3274"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Smith, Colin A."],["dc.contributor.author","Ban, David"],["dc.contributor.author","Pratihar, Supriya"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Paulat, Maria"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Lee, Donghan"],["dc.contributor.author","Groot, Bert L. de"],["dc.date.accessioned","2017-09-07T11:54:34Z"],["dc.date.available","2017-09-07T11:54:34Z"],["dc.date.issued","2016"],["dc.description.abstract","Many biological processes depend on allosteric communication between different parts of a protein, but the role of internal protein motion in propagating signals through the structure remains largely unknown. Through an experimental and computational analysis of the ground state dynamics in ubiquitin, we identify a collective global motion that is specifically linked to a conformational switch distant from the binding interface. This allosteric coupling is also present in crystal structures and is found to facilitate multispecificity, particularly binding to the ubiquitin-specific protease (USP) family of deubiquitinases. The collective motion that enables this allosteric communication does not affect binding through localized changes but, instead, depends on expansion and contraction of the entire protein domain. The characterization of these collective motions represents a promising avenue for finding and manipulating allosteric networks."],["dc.identifier.doi","10.1073/pnas.1519609113"],["dc.identifier.gro","3141707"],["dc.identifier.isi","000372488200052"],["dc.identifier.pmid","26961002"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/180"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","Allosteric switch regulates protein-protein binding through collective motion"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]