Matthes, Dirk

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Frieg, Benedikt"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Dienemann, Christian"],["dc.contributor.author","Geraets, James A."],["dc.contributor.author","Najbauer, Eszter E."],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.author","Andreas, Loren B."],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Schröder, Gunnar F."],["dc.date.accessioned","2022-12-01T08:30:50Z"],["dc.date.available","2022-12-01T08:30:50Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n α-synuclein misfolding and aggregation into fibrils is a common feature of α-synucleinopathies, such as Parkinson’s disease, in which α-synuclein fibrils are a characteristic hallmark of neuronal inclusions called Lewy bodies. Studies on the composition of Lewy bodies extracted postmortem from brain tissue of Parkinson’s patients revealed that lipids and membranous organelles are also a significant component. Interactions between α-synuclein and lipids have been previously identified as relevant for Parkinson’s disease pathology, however molecular insights into their interactions have remained elusive. Here we present cryo-electron microscopy structures of six α-synuclein fibrils in complex with lipids, revealing specific lipid-fibril interactions. We observe that phospholipids promote an alternative protofilament fold, mediate an unusual arrangement of protofilaments, and fill the central cavities of the fibrils. Together with our previous studies, these structures also indicate a mechanism for fibril-induced lipid extraction, which is likely to be involved in the development of α-synucleinopathies. Specifically, one potential mechanism for the cellular toxicity is the disruption of intracellular vesicles mediated by fibrils and oligomers, and therefore the modulation of these interactions may provide a promising strategy for future therapeutic interventions."],["dc.identifier.doi","10.1038/s41467-022-34552-7"],["dc.identifier.pii","34552"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/117993"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.relation.eissn","2041-1723"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The 3D structure of lipidic fibrils of α-synuclein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Brennecke, Julian T."],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T08:58:33Z"],["dc.date.available","2021-03-05T08:58:33Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1038/srep33156"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80179"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.eissn","2045-2322"],["dc.title","An Atomistic View of Amyloidogenic Self-assembly: Structure and Dynamics of Heterogeneous Conformational States in the Pre-nucleation Phase"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","650a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","98"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T08:57:50Z"],["dc.date.available","2021-03-05T08:57:50Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1016/j.bpj.2009.12.3561"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79901"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.issn","0006-3495"],["dc.title","The Spontaneous Aggregation of Steric Zipper Peptides Studied by Molecular Dynamics Simulations"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","402a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","110"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Brennecke, Julian T."],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T08:58:00Z"],["dc.date.available","2021-03-05T08:58:00Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1016/j.bpj.2015.11.2170"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79964"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.issn","0006-3495"],["dc.title","Global and Local Conformational Heterogeniety Governs the Pre-Nucleation Phase in Amyloidogenic Self-Assembly"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","e19129"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","PLoS One"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Daebel, Venita"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.editor","Pastore, Annalisa"],["dc.date.accessioned","2021-03-05T08:59:12Z"],["dc.date.available","2021-03-05T08:59:12Z"],["dc.date.issued","2011"],["dc.identifier.doi","10.1371/journal.pone.0019129"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80396"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.eissn","1932-6203"],["dc.title","Mapping the Conformational Dynamics and Pathways of Spontaneous Steric Zipper Peptide Oligomerization"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2791"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","ASC Chemical Neuroscience"],["dc.bibliographiccitation.lastpage","2808"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2018-01-17T11:26:28Z"],["dc.date.available","2018-01-17T11:26:28Z"],["dc.date.issued","2017"],["dc.description.abstract","The diphenyl-pyrazole compound anle138b is a known inhibitor of oligomeric aggregate formation in vitro and in vivo. Therefore, anle138b is considered a promising drug candidate to beneficially interfere with neurodegenerative processes causing devastating pathologies in humans. The atomistic details of the aggregation inhibition mechanism, however, are to date unknown since the ensemble of small nonfibrillar aggregates is structurally heterogeneous and inaccessible to direct structural characterization. Here, we set out to elucidate anle138b's mode of action using all-atom molecular dynamics simulations on the multi-microsecond time scale. By comparing simulations of dimeric to tetrameric aggregates from fragments of four amyloidogenic proteins (Aβ, hTau40, hIAPP, and Sup35N) in the presence and absence of anle138b, we show that the compound reduces the overall number of intermolecular hydrogen bonds, disfavors the sampling of the aggregated state, and remodels the conformational distributions within the small oligomeric peptide aggregates. Most notably, anle138b preferentially interacts with the disordered structure ensemble via its pyrazole moiety, thereby effectively blocking interpeptide main chain interactions and impeding the spontaneous formation of ordered β-sheet structures, in particular those with out-of-register antiparallel β-strands. The structurally very similar compound anle234b was previously identified as inactive by in vitro experiments. Here, we show that anle234b has no significant effect on the aggregation process in terms of reducing the β-structure content. Moreover, we demonstrate that the hydrogen bonding capabilities are autoinhibited due to steric effects imposed by the molecular geometry of anle234b and thereby indirectly confirm the proposed inhibitory mechanism of anle138b. We anticipate that the prominent binding of anle138b to partially disordered and dynamical aggregate structures is a generic basis for anle138b's ability to suppress toxic oligomer formation in a wide range of amyloidogenic peptides and proteins."],["dc.identifier.doi","10.1021/acschemneuro.7b00325"],["dc.identifier.pmid","28906103"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11674"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1948-7193"],["dc.title","Resolving the Atomistic Modes of Anle138b Inhibitory Action on Peptide Oligomer Formation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","599"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.lastpage","608"],["dc.bibliographiccitation.volume","97"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T09:05:26Z"],["dc.date.available","2021-03-05T09:05:26Z"],["dc.date.issued","2009"],["dc.identifier.doi","10.1016/j.bpj.2009.04.061"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80474"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.issn","0006-3495"],["dc.title","Secondary Structure Propensities in Peptide Folding Simulations: A Systematic Comparison of Molecular Mechanics Interaction Schemes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","390"],["dc.bibliographiccitation.issue","2-3"],["dc.bibliographiccitation.journal","Journal of Molecular Biology"],["dc.bibliographiccitation.lastpage","416"],["dc.bibliographiccitation.volume","421"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Gapsys, Vytautas"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2021-03-05T08:58:08Z"],["dc.date.available","2021-03-05T08:58:08Z"],["dc.date.issued","2012"],["dc.identifier.doi","10.1016/j.jmb.2012.02.004"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80019"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-393"],["dc.relation.issn","0022-2836"],["dc.title","Driving Forces and Structural Determinants of Steric Zipper Peptide Oligomer Formation Elucidated by Atomistic Simulations"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","362"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Molecular Biology"],["dc.bibliographiccitation.lastpage","376"],["dc.bibliographiccitation.volume","426"],["dc.contributor.author","Matthes, Dirk"],["dc.contributor.author","Daebel, Venita"],["dc.contributor.author","Meyenberg, Karsten"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Heim, Gudrun"],["dc.contributor.author","Diederichsen, Ulf"],["dc.contributor.author","Lange, Adam"],["dc.contributor.author","de Groot, Bert L."],["dc.date.accessioned","2018-11-07T09:45:03Z"],["dc.date.available","2018-11-07T09:45:03Z"],["dc.date.issued","2014"],["dc.description.abstract","Recently, several short peptides have been shown to self-assemble into amyloid fibrils with generic cross-beta spines, so-called steric zippers, suggesting common underlying structural features and aggregation mechanisms. Understanding these mechanisms is a prerequisite,for designing fibril-binding compounds and inhibitors of fibril formation. The hexapeptide VEALYL, corresponding to the residues B12-17 of full-length insulin, has been identified as one of these short segments. Here, we analyzed the structures of multiple, morphologically different (fibrillar, microcrystal-like, oligomeric) [C-13,N-15]VEALYL samples by solid-state nuclear magnetic resonance complemented with results from molecular dynamics simulations. By performing NHHC/CHHC experiments, we could determine that the beta-strands within a given sheet of the amyloid-like fibrils formed by the insulin hexapeptide VEALYL are stacked in an antiparallel manner, whereas the sheet-to-sheet packing arrangement was found to be parallel. Experimentally observed secondary chemical shifts for all aggregate forms, as well as empty set and Psi backbone torsion angles calculated with TALOS, are indicative of beta-strand conformation, consistent with the published crystal structure (PDB ID: 2OMQ). Thus, we could demonstrate that the structural features of all the observed VEALYL aggregates are in agreement with the previously observed homosteric zipper spine packing in the crystalline state, suggesting that several distinct aggregate morphologies share the same molecular architecture. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.jmb.2013.10.020"],["dc.identifier.isi","000330148100009"],["dc.identifier.pmid","24513105"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/11363"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/34531"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Ltd- Elsevier Science Ltd"],["dc.relation.issn","1089-8638"],["dc.relation.issn","0022-2836"],["dc.rights","CC BY-NC-SA 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-sa/3.0"],["dc.title","Spontaneous Aggregation of the Insulin-Derived Steric Zipper Peptide VEALYL Results in Different Aggregation Forms with Common Features"],["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"]]