Villinger, Saskia

[["dc.bibliographiccitation.firstpage","10518"],["dc.bibliographiccitation.issue","35"],["dc.bibliographiccitation.journal","Angewandte Chemie International Edition"],["dc.bibliographiccitation.lastpage","10521"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Jaremko, Mariusz"],["dc.contributor.author","Jaremko, Lukasz"],["dc.contributor.author","Villinger, Saskia"],["dc.contributor.author","Schmidt, Christian D."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:44:43Z"],["dc.date.available","2017-09-07T11:44:43Z"],["dc.date.issued","2016"],["dc.description.abstract","N-15 spin-relaxation rates are demonstrated to provide critical information about the long-range structure and internal motions of membrane proteins. Combined with an improved calculation method, the relaxation-rate-derived structure of the 283-residue human voltage-dependent anion channel revealed an anisotropically shaped barrel with a rigidly attached N-terminal helix. Our study thus establishes an NMR spectroscopic approach to determine the structure and dynamics of mammalian membrane proteins at high accuracy and resolution."],["dc.identifier.doi","10.1002/anie.201602639"],["dc.identifier.gro","3141634"],["dc.identifier.isi","000383373700065"],["dc.identifier.pmid","27461260"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3567"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.eissn","1521-3773"],["dc.relation.issn","1433-7851"],["dc.title","High-Resolution NMR Determination of the Dynamic Structure of Membrane Proteins"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13397"],["dc.bibliographiccitation.issue","19"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","13406"],["dc.bibliographiccitation.volume","289"],["dc.contributor.author","Villinger, Saskia"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Bayrhuber, Monika"],["dc.contributor.author","Lange, Adam"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:46:15Z"],["dc.date.available","2017-09-07T11:46:15Z"],["dc.date.issued","2014"],["dc.description.abstract","Background: Human VDAC1 mediates and controls the transport of metabolites across the outer mitochondrial membrane. Results: The N-terminal helix of hVDAC1 is involved in binding to charged forms of ATP, UTP, and GTP with an important contribution from lysine 20. Conclusion: Weak binding of ATP confers specificity for ATP transport. Significance: ATP interaction mapped at residue resolution supports metabolite selectivity of VDAC. The voltage-dependent anion channel (VDAC) mediates and gates the flux of metabolites and ions across the outer mitochondrial membrane and is a key player in cellular metabolism and apoptosis. Here we characterized the binding of nucleotides to human VDAC1 (hVDAC1) on a single-residue level using NMR spectroscopy and site-directed mutagenesis. We find that hVDAC1 possesses one major binding region for ATP, UTP, and GTP that partially overlaps with a previously determined NADH binding site. This nucleotide binding region is formed by the N-terminal -helix, the linker connecting the helix to the first -strand and adjacent barrel residues. hVDAC1 preferentially binds the charged forms of ATP, providing support for a mechanism of metabolite transport in which direct binding to the charged form exerts selectivity while at the same time permeation of the Mg2+-complexed ATP form is possible."],["dc.identifier.doi","10.1074/jbc.M113.524173"],["dc.identifier.gro","3142126"],["dc.identifier.isi","000335522800038"],["dc.identifier.pmid","24668813"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/4833"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.eissn","1083-351X"],["dc.relation.issn","0021-9258"],["dc.title","Nucleotide Interactions of the Human Voltage-dependent Anion Channel"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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","15370"],["dc.bibliographiccitation.issue","40"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","15375"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Bayrhuber, Monika"],["dc.contributor.author","Meins, Thomas"],["dc.contributor.author","Habeck, Michael"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Villinger, Saskia"],["dc.contributor.author","Vonrhein, Clemens"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Zeth, Kornelius"],["dc.date.accessioned","2017-09-07T11:48:11Z"],["dc.date.available","2017-09-07T11:48:11Z"],["dc.date.issued","2008"],["dc.description.abstract","The voltage-dependent anion channel (VDAC), also known as mitochondrial porin, is the most abundant protein in the mitochondrial outer membrane (MOM). VDAC is the channel known to guide the metabolic flux across the MOM and plays a key role in mitochondrially induced apoptosis. Here, we present the 3D structure of human VDAC1, which was solved conjointly by NMR spectroscopy and x-ray crystallography. Human VDAC1 (hVDAC1) adopts a beta-barrel architecture composed of 19 beta-strands with an a-helix located horizontally midway within the pore. Bioinformatic analysis indicates that this channel architecture is common to all VDAC proteins and is adopted by the general import pore TOM40 of mammals, which is also located in the MOM."],["dc.identifier.doi","10.1073/pnas.0808115105"],["dc.identifier.gro","3143227"],["dc.identifier.isi","000260360500030"],["dc.identifier.pmid","18832158"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/718"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Structure of the human voltage-dependent anion channel"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","22546"],["dc.bibliographiccitation.issue","52"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","22551"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Villinger, Saskia"],["dc.contributor.author","Briones, Rodolfo"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Zachariae, Ulrich"],["dc.contributor.author","Lange, Adam"],["dc.contributor.author","Groot, Bert L. de"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:45:10Z"],["dc.date.available","2017-09-07T11:45:10Z"],["dc.date.issued","2010"],["dc.description.abstract","The voltage-dependent anion channel (VDAC), located in the outer mitochondrial membrane, acts as a gatekeeper for the entry and exit of mitochondrial metabolites. Here we reveal functional dynamics of isoform one of VDAC (VDAC1) by a combination of solution NMR spectroscopy, Gaussian network model analysis, and molecular dynamics simulation. Micro-to millisecond dynamics are significantly increased for the N-terminal six beta-strands of VDAC1 in micellar solution, in agreement with increased B-factors observed in the same region in the bicellar crystal structure of VDAC1. Molecular dynamics simulations reveal that a charge on the membrane-facing glutamic acid 73 (E73) accounts for the elevation of N-terminal protein dynamics as well as a thinning of the nearby membrane. Mutation or chemical modification of E73 strongly reduces the micro-to millisecond dynamics in solution. Because E73 is necessary for hexokinase-I-induced VDAC channel closure and inhibition of apoptosis, our results imply that micro- to millisecond dynamics in the N-terminal part of the barrel are essential for VDAC interaction and gating."],["dc.identifier.doi","10.1073/pnas.1012310108"],["dc.identifier.gro","3142815"],["dc.identifier.isi","000285684200039"],["dc.identifier.pmid","21148773"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/261"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Natl Acad Sciences"],["dc.relation.issn","0027-8424"],["dc.title","Functional dynamics in the voltage-dependent anion channel"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","585"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Structure"],["dc.bibliographiccitation.lastpage","594"],["dc.bibliographiccitation.volume","24"],["dc.contributor.author","Ge, Lin"],["dc.contributor.author","Villinger, Saskia"],["dc.contributor.author","Mari, Stefania A."],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Müller, Daniel J."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:54:33Z"],["dc.date.available","2017-09-07T11:54:33Z"],["dc.date.issued","2016"],["dc.description.abstract","The voltage-dependent anion channel (VDAC) regulates the flux of metabolites and ions across the outer mitochondrial membrane. Regulation of ion flow involves conformational transitions in VDAC, but the nature of these changes has not been resolved to date. By combining single-molecule force spectroscopy with nuclear magnetic resonance spectroscopy we show that the beta barrel of human VDAC embedded into a membrane is highly flexible. Its mechanical flexibility exceeds by up to one order of magnitude that determined for beta strands of other membrane proteins and is largest in the N-terminal part of the b barrel. Interaction with Ca2+, a key regulator of metabolism and apoptosis, considerably decreases the barrel's conformational variability and kinetic free energy in the membrane. The combined data suggest that physiological VDAC function depends on the molecular plasticity of its channel."],["dc.identifier.doi","10.1016/j.str.2016.02.012"],["dc.identifier.gro","3141699"],["dc.identifier.isi","000373568700014"],["dc.identifier.pmid","27021164"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/91"],["dc.language.iso","en"],["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","Molecular Plasticity of the Human Voltage-Dependent Anion Channel Embedded Into a Membrane"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]