Zweckstetter, Markus

[["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.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.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.artnumber","jnc.15461"],["dc.bibliographiccitation.firstpage","554"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Neurochemistry"],["dc.bibliographiccitation.lastpage","573"],["dc.bibliographiccitation.volume","159"],["dc.contributor.affiliation","Dauer née Joppe, Karina; 1Department of Neurology University Medical Center Goettingen Goettingen Germany"],["dc.contributor.affiliation","Caldi Gomes, Lucas; 1Department of Neurology University Medical Center Goettingen Goettingen Germany"],["dc.contributor.affiliation","Zhang, Shuyu; 3Department of Neurology School of Medicine University Hospital rechts der IsarTechnical University of Munich Munich Germany"],["dc.contributor.affiliation","Parvaz, Mojan; 3Department of Neurology School of Medicine University Hospital rechts der IsarTechnical University of Munich Munich Germany"],["dc.contributor.affiliation","Carboni, Eleonora; 1Department of Neurology University Medical Center Goettingen Goettingen Germany"],["dc.contributor.affiliation","Roser, Anna‐Elisa; 1Department of Neurology University Medical Center Goettingen Goettingen Germany"],["dc.contributor.affiliation","El DeBakey, Hazem; 4Department of Neurology University Hospital of Wuerzburg Wuerzburg Germany"],["dc.contributor.affiliation","Bähr, Mathias; 1Department of Neurology University Medical Center Goettingen Goettingen Germany"],["dc.contributor.affiliation","Vogel‐Mikuš, Katarina; 6Biotechnical faculty University of Ljubljana Ljubljana Slovenia"],["dc.contributor.affiliation","Wang Ip, Chi; 4Department of Neurology University Hospital of Wuerzburg Wuerzburg Germany"],["dc.contributor.affiliation","Becker, Stefan; 8Department of NMR Based Structural BiologyMax Planck Institute for Biophysical Chemistry Goettingen Germany"],["dc.contributor.affiliation","Zweckstetter, Markus; 1Department of Neurology University Medical Center Goettingen Goettingen Germany"],["dc.contributor.author","Tatenhorst, Lars"],["dc.contributor.author","Caldi Gomes, Lucas"],["dc.contributor.author","Zhang, Shuyu"],["dc.contributor.author","Parvaz, Mojan"],["dc.contributor.author","Carboni, Eleonora"],["dc.contributor.author","Roser, Anna‐Elisa"],["dc.contributor.author","El DeBakey, Hazem"],["dc.contributor.author","Bähr, Mathias"],["dc.contributor.author","Lingor, Paul"],["dc.contributor.author","Dauer née Joppe, Karina"],["dc.contributor.author","Vogel‐Mikuš, Katarina"],["dc.contributor.author","Wang Ip, Chi"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2021-07-05T14:57:43Z"],["dc.date.available","2021-07-05T14:57:43Z"],["dc.date.issued","2021"],["dc.date.updated","2022-03-21T09:42:08Z"],["dc.description.abstract","Abstract Regional iron accumulation and α‐synuclein (α‐syn) spreading pathology within the central nervous system are common pathological findings in Parkinson's disease (PD). Whereas iron is known to bind to α‐syn, facilitating its aggregation and regulating α‐syn expression, it remains unclear if and how iron also modulates α‐syn spreading. To elucidate the influence of iron on the propagation of α‐syn pathology, we investigated α‐syn spreading after stereotactic injection of α‐syn preformed fibrils (PFFs) into the striatum of mouse brains after neonatal brain iron enrichment. C57Bl/6J mouse pups received oral gavage with 60, 120, or 240 mg/kg carbonyl iron or vehicle between postnatal days 10 and 17. At 12 weeks of age, intrastriatal injections of 5‐µg PFFs were performed to induce seeding of α‐syn aggregates. At 90 days post‐injection, PFFs‐injected mice displayed long‐term memory deficits, without affection of motor behavior. Interestingly, quantification of α‐syn phosphorylated at S129 showed reduced α‐syn pathology and attenuated spreading to connectome‐specific brain regions after brain iron enrichment. Furthermore, PFFs injection caused intrastriatal microglia accumulation, which was alleviated by iron in a dose‐dependent way. In primary cortical neurons in a microfluidic chamber model in vitro, iron application did not alter trans‐synaptic α‐syn propagation, possibly indicating an involvement of non‐neuronal cells in this process. Our study suggests that α‐syn PFFs may induce cognitive deficits in mice independent of iron. However, a redistribution of α‐syn aggregate pathology and reduction of striatal microglia accumulation in the mouse brain may be mediated via iron‐induced alterations of the brain connectome. image"],["dc.description.abstract","Brain iron accumulation and α‐synuclein (α‐syn) spreading pathology are common pathological findings in Parkinson's disease. To elucidate the influence of iron on α‐syn propagation, we investigated α‐syn spreading after stereotactic injection of α‐syn preformed fibrils (PFFs) into the striatum of C57Bl/6 mice after neonatal brain iron enrichment. 90 days post‐injection, PFFs injected mice displayed memory deficits, reduced α‐syn pathology and spreading to connectome‐specific regions after brain iron enrichment. Our study suggests that α‐syn PFFs may induce cognitive deficits in mice independent of iron. However, a redistribution of α‐syn pathology may be mediated via iron‐induced alterations of the brain connectome. image"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship","MPI"],["dc.identifier.doi","10.1111/jnc.15461"],["dc.identifier.pmid","34176164"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87716"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/315"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-441"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1471-4159"],["dc.relation.issn","0022-3042"],["dc.relation.workinggroup","RG Bähr (Neurobiological Research Laboratory)"],["dc.rights","This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made."],["dc.title","Brain iron enrichment attenuates α‐synuclein spreading after injection of preformed fibrils"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","12545"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Wysoczanski, Piotr"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T09:54:29Z"],["dc.date.available","2018-11-07T09:54:29Z"],["dc.date.issued","2015"],["dc.description.abstract","The action of the spliceosome depends on the stepwise cooperative assembly and disassembly of its components. Very strong cooperativity was observed for the RES (Retention and Splicing) heterotrimeric complex where the affinity from binary to tertiary interactions changes more than 100-fold and affects RNA binding. The RES complex is involved in splicing regulation and retention of not properly spliced pre-mRNA with its three components-Snu17p, Pml1p and Bud13p-giving rise to the two possible intermediate dimeric complexes Pml1p-Snu17p and Bud13p-Snu17p. Here we determined the three-dimensional structure and dynamics of the Pml1p-Snu17p and Bud13p-Snu17p dimers using liquid state NMR. We demonstrate that localized as well as global changes occur along the RES trimer assembly pathway. The stepwise rigidification of the Snu17p structure following the binding of Pml1p and Bud13p provides a basis for the strong cooperative nature of RES complex assembly."],["dc.identifier.doi","10.1038/srep12545"],["dc.identifier.isi","000358542400001"],["dc.identifier.pmid","26212312"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13632"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36543"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Structures of intermediates during RES complex assembly"],["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.artnumber","e1001577"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Aggarwal, Shweta"],["dc.contributor.author","Snaidero, Nicolas"],["dc.contributor.author","Paehler, Gesa"],["dc.contributor.author","Frey, Steffen"],["dc.contributor.author","Sanchez, Paula"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Janshoff, Andreas"],["dc.contributor.author","Schneider, Anja"],["dc.contributor.author","Weil, Marie-Theres"],["dc.contributor.author","Schaap, Iwan Alexander Taco"],["dc.contributor.author","Goerlich, Dirk"],["dc.contributor.author","Simons, Mikael"],["dc.date.accessioned","2018-11-07T09:23:52Z"],["dc.date.available","2018-11-07T09:23:52Z"],["dc.date.issued","2013"],["dc.description.abstract","Rapid conduction of nerve impulses requires coating of axons by myelin. To function as an electrical insulator, myelin is generated as a tightly packed, lipid-rich multilayered membrane sheath. Knowledge about the mechanisms that govern myelin membrane biogenesis is required to understand myelin disassembly as it occurs in diseases such as multiple sclerosis. Here, we show that myelin basic protein drives myelin biogenesis using weak forces arising from its inherent capacity to phase separate. The association of myelin basic protein molecules to the inner leaflet of the membrane bilayer induces a phase transition into a cohesive mesh-like protein network. The formation of this protein network shares features with amyloid fibril formation. The process is driven by phenylalanine-mediated hydrophobic and amyloid-like interactions that provide the molecular basis for protein extrusion and myelin membrane zippering. These findings uncover a physicochemical mechanism of how a cytosolic protein regulates the morphology of a complex membrane architecture. These results provide a key mechanism in myelin membrane biogenesis with implications for disabling demyelinating diseases of the central nervous system."],["dc.description.sponsorship","ERC Starting Grant; German Research Foundation [SI 746/9-1, TRR43]"],["dc.identifier.doi","10.1371/journal.pbio.1001577"],["dc.identifier.fs","600727"],["dc.identifier.isi","000321042900005"],["dc.identifier.pmid","23762018"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9108"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29688"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation.issn","1545-7885"],["dc.relation.orgunit","Fakultät für Physik"],["dc.rights","CC BY-NC-ND 3.0"],["dc.rights.uri","http://creativecommons.org/licenses/by-nc-nd/3.0/"],["dc.title","Myelin Membrane Assembly Is Driven by a Phase Transition of Myelin Basic Proteins Into a Cohesive Protein Meshwork"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","e1000034"],["dc.bibliographiccitation.firstpage","399"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","PLoS Biology"],["dc.bibliographiccitation.lastpage","414"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Mukrasch, Marco D."],["dc.contributor.author","Bibow, Stefan"],["dc.contributor.author","Korukottu, Jegannath"],["dc.contributor.author","Jeganathan, Sadasivam"],["dc.contributor.author","Biernat, Jacek"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Mandelkow, Eckhard"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:47:34Z"],["dc.date.available","2017-09-07T11:47:34Z"],["dc.date.issued","2009"],["dc.description.abstract","Alzheimer disease is characterized by abnormal protein deposits in the brain, such as extracellular amyloid plaques and intracellular neurofibrillary tangles. The tangles are made of a protein called tau comprising 441 residues in its longest isoform. Tau belongs to the class of natively unfolded proteins, binds to and stabilizes microtubules, and partially folds into an ordered beta-structure during aggregation to Alzheimer paired helical filaments (PHFs). Here we show that it is possible to overcome the size limitations that have traditionally hampered detailed nuclear magnetic resonance (NMR) spectroscopy studies of such large nonglobular proteins. This is achieved using optimal NMR pulse sequences and matching of chemical shifts from smaller segments in a divide and conquer strategy. The methodology reveals that 441-residue tau is highly dynamic in solution with a distinct domain character and an intricate network of transient long-range contacts important for pathogenic aggregation. Moreover, the single-residue view provided by the NMR analysis reveals unique insights into the interaction of tau with microtubules. Our results establish that NMR spectroscopy can provide detailed insight into the structural polymorphism of very large nonglobular proteins."],["dc.identifier.doi","10.1371/journal.pbio.1000034"],["dc.identifier.gro","3143159"],["dc.identifier.isi","000263599900018"],["dc.identifier.pmid","19226187"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8445"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/642"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Public Library Science"],["dc.relation.issn","1544-9173"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","Structural Polymorphism of 441-Residue Tau at Single Residue Resolution"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","14893"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Jaipuria, Garima"],["dc.contributor.author","Leonov, Andrei"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Vasa, Suresh Kumar"],["dc.contributor.author","Jaremko, Lukasz"],["dc.contributor.author","Jaremko, Mariusz"],["dc.contributor.author","Linser, Rasmus"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2018-11-07T10:26:01Z"],["dc.date.available","2018-11-07T10:26:01Z"],["dc.date.issued","2017"],["dc.description.abstract","Cholesterol is an important regulator of membrane protein function. However, the exact mechanisms involved in this process are still not fully understood. Here we study how the tertiary and quaternary structure of the mitochondrial translocator protein TSPO, which binds cholesterol with nanomolar affinity, is affected by this sterol. Residue-specific analysis of TSPO by solid-state NMR spectroscopy reveals a dynamic monomer-dimer equilibrium of TSPO in the membrane. Binding of cholesterol to TSPO's cholesterol-recognition motif leads to structural changes across the protein that shifts the dynamic equilibrium towards the translocator monomer. Consistent with an allosteric mechanism, a mutation within the oligomerization interface perturbs transmembrane regions located up to 35 angstrom away from the interface, reaching TSPO's cholesterol-binding motif. The lower structural stability of the intervening transmembrane regions provides a mechanistic basis for signal transmission. Our study thus reveals an allosteric signal pathway that connects membrane protein tertiary and quaternary structure with cholesterol binding."],["dc.identifier.doi","10.1038/ncomms14893"],["dc.identifier.isi","000397799000001"],["dc.identifier.pmid","28358007"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14416"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42959"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Cholesterol-mediated allosteric regulation of the mitochondrial translocator protein structure"],["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.artnumber","2909"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Ukmar-Godec, Tina"],["dc.contributor.author","Hutten, Saskia"],["dc.contributor.author","Grieshop, Matthew P."],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Cima-Omori, Maria-Sol"],["dc.contributor.author","Biernat, Jacek"],["dc.contributor.author","Mandelkow, Eckhard"],["dc.contributor.author","Söding, Johannes"],["dc.contributor.author","Dormann, Dorothee"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2019-07-22T12:49:00Z"],["dc.date.available","2019-07-22T12:49:00Z"],["dc.date.issued","2019-07-02"],["dc.description.abstract","Cells form and use biomolecular condensates to execute biochemical reactions. The molecular properties of non-membrane-bound condensates are directly connected to the amino acid content of disordered protein regions. Lysine plays an important role in cellular function, but little is known about its role in biomolecular condensation. Here we show that protein disorder is abundant in protein/RNA granules and lysine is enriched in disordered regions of proteins in P-bodies compared to the entire human disordered proteome. Lysine-rich polypeptides phase separate into lysine/RNA-coacervates that are more dynamic and differ at the molecular level from arginine/RNA-coacervates. Consistent with the ability of lysine to drive phase separation, lysine-rich variants of the Alzheimer's disease-linked protein tau undergo coacervation with RNA in vitro and bind to stress granules in cells. Acetylation of lysine reverses liquid-liquid phase separation and reduces colocalization of tau with stress granules. Our study establishes lysine as an important regulator of cellular condensation."],["dc.identifier.doi","10.1038/s41467-019-10792-y"],["dc.identifier.pmid","31266957"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16293"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/61798"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","2041-1723"],["dc.relation.issn","2041-1723"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Lysine/RNA-interactions drive and regulate biomolecular condensation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","111"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Biomolecular NMR"],["dc.bibliographiccitation.lastpage","119"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Gruene, Tim"],["dc.contributor.author","Cho, Min-Kyu"],["dc.contributor.author","Karyagina, Irina"],["dc.contributor.author","Kim, Hai-Young"],["dc.contributor.author","Grosse, Christian"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Becker, Stefan"],["dc.date.accessioned","2018-11-07T08:59:23Z"],["dc.date.available","2018-11-07T08:59:23Z"],["dc.date.issued","2011"],["dc.description.abstract","Long-range structural information derived from paramagnetic relaxation enhancement observed in the presence of a paramagnetic nitroxide radical is highly useful for structural characterization of globular, modular and intrinsically disordered proteins, as well as protein protein and protein-DNA complexes. Here we characterized the conformation of a spin-label attached to the homodimeric protein CylR2 using a combination of X-ray crystallography, electron paramagnetic resonance (EPR) and NMR spectroscopy. Close agreement was found between the conformation of the spin label observed in the crystal structure with interspin distances measured by EPR and signal broadening in NMR spectra, suggesting that the conformation seen in the crystal structure is also preferred in solution. In contrast, conformations of the spin label observed in crystal structures of T4 lysozyme are not in agreement with the paramagnetic relaxation enhancement observed for spin-labeled CylR2 in solution. Our data demonstrate that accurate positioning of the paramagnetic center is essential for high-resolution structure determination."],["dc.description.sponsorship","Max Planck Society; Fonds der Chemischen Industrie; DFG [ZW 71/2-2, 3-2]"],["dc.identifier.doi","10.1007/s10858-011-9471-y"],["dc.identifier.isi","000288768700006"],["dc.identifier.pmid","21271275"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6660"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23880"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0925-2738"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Integrated analysis of the conformation of a protein-linked spin label by crystallography, EPR and NMR spectroscopy"],["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"]]