Giller, Karin

[["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.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"]]

[["dc.bibliographiccitation.firstpage","1223"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.lastpage","1234"],["dc.bibliographiccitation.volume","111"],["dc.contributor.author","Briones, Rodolfo"],["dc.contributor.author","Weichbrodt, Conrad"],["dc.contributor.author","Paltrinieri, Licia"],["dc.contributor.author","Mey, Ingo"],["dc.contributor.author","Villinger, Saskia"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Lange, Adam"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Steinem, Claudia"],["dc.contributor.author","De Groot, Bert L."],["dc.date.accessioned","2017-09-07T11:44:37Z"],["dc.date.available","2017-09-07T11:44:37Z"],["dc.date.issued","2016"],["dc.description.abstract","The voltage-dependent anion channel 1 (VDAC-1) is an important protein of the outer mitochondria! membrane that transports energy metabolites and is involved in apoptosis. The available structures of VDAC proteins show a wide beta-stranded barrel pore, with its N-terminal alpha-helix (N-alpha) bound to its interior. Electrophysiology experiments revealed that voltage, its polarity, and membrane composition modulate VDAC currents. Experiments with VDAC-1 mutants identified amino acids that regulate the gating process. However, the mechanisms for how these factors regulate VDAC-1, and which changes they trigger in the channel, are still unknown. In this study, molecular dynamics simulations and single-channel experiments of VDAC-1 show agreement for the current-voltage relationships of an \"open\" channel and they also show several subconducting transient states that are more cation selective in the simulations. We observed voltage-dependent asymmetric distortions of the VDAC-1 barrel and the displacement of particular charged amino acids. We constructed conformational models of the protein voltage response and the pore changes that consistently explain the protein conformations observed at opposite voltage polarities, either in phosphatidylethanolamine or phosphatidylcholine membranes. The submicrosecond VDAC-1 voltage response shows intrinsic structural changes that explain the role of key gating amino acids and support some of the current gating hypotheses. These voltage-dependent protein changes include asymmetric barrel distortion, its interaction with the membrane, and significant displacement of N-alpha amino acids."],["dc.identifier.doi","10.1016/j.bpj.2016.08.007"],["dc.identifier.gro","3141619"],["dc.identifier.isi","000383925700015"],["dc.identifier.pmid","27653481"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13769"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1900"],["dc.language.iso","en"],["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.relation.eissn","1542-0086"],["dc.relation.issn","0006-3495"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.title","Voltage Dependence of Conformational Dynamics and Subconducting States of VDAC-1"],["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.firstpage","27582"],["dc.bibliographiccitation.issue","46"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","27593"],["dc.bibliographiccitation.volume","290"],["dc.contributor.author","Moree, Ben"],["dc.contributor.author","Yin, Guowei"],["dc.contributor.author","Lazaro, Diana F."],["dc.contributor.author","Munari, Francesca"],["dc.contributor.author","Strohaeker, Timo"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Outeiro, Tiago Fleming"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Salafsky, Joshua"],["dc.date.accessioned","2018-11-07T09:48:56Z"],["dc.date.available","2018-11-07T09:48:56Z"],["dc.date.issued","2015"],["dc.description.abstract","Proteins are structurally dynamic molecules that perform specialized functions through unique conformational changes accessible in physiological environments. An ability to specifically and selectively control protein function via conformational modulation is an important goal for development of novel therapeutics and studies of protein mechanism in biological networks and disease. Here we applied a second-harmonic generation-based technique for studying protein conformation in solution and in real time to the intrinsically disordered, Parkinson disease related protein alpha-synuclein. From a fragment library, we identified small molecule modulators that bind to monomeric alpha-synuclein in vitro and significantly reduce alpha-synuclein aggregation in a neuronal cell culture model. Our results indicate that the conformation of alpha-synuclein is linked to the aggregation of protein in cells. They also provide support for a therapeutic strategy of targeting specific conformations of the protein to suppress or control its aggregation."],["dc.identifier.doi","10.1074/jbc.M114.636027"],["dc.identifier.isi","000365757500014"],["dc.identifier.pmid","26396193"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12741"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35410"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Small Molecules Detected by Second-Harmonic Generation Modulate the Conformation of Monomeric alpha-Synuclein and Reduce Its Aggregation in Cells"],["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"]]