Gräter, Frauke

[["dc.bibliographiccitation.firstpage","2687"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","ChemPhysChem"],["dc.bibliographiccitation.lastpage","2697"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Li, Wenjin"],["dc.contributor.author","Edwards, Scott A."],["dc.contributor.author","Lu, Lanyuan"],["dc.contributor.author","Kubar, Tomas"],["dc.contributor.author","Patil, Sandeep P."],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Groenhof, Gerrit"],["dc.contributor.author","Gräter, Frauke"],["dc.date.accessioned","2018-02-12T11:05:37Z"],["dc.date.available","2018-02-12T11:05:37Z"],["dc.date.issued","2013"],["dc.description.abstract","Internal molecular forces can guide chemical reactions, yet are not straightforwardly accessible within a quantum mechanical description of the reacting molecules. Here, we present a force-matching force distribution analysis (FM-FDA) to analyze internal forces in molecules. We simulated the ring opening of trans-3,4-dimethylcyclobutene (tDCB) with on-the-fly semiempirical molecular dynamics. The self-consistent density functional tight binding (SCC-DFTB) method accurately described the force-dependent ring-opening kinetics of tDCB, showing quantitative agreement with both experimental and computational data at higher levels. Mechanical force was applied in two different ways, namely, externally by a constant pulling force and internally by embedding tDCB within a strained macrocycle-containing stiff stilbene. We analyzed the distribution of tDCB internal forces in the two different cases by FM-FDA and found that external force gave rise to a symmetric force distribution in the cyclobutene ring, which also scaled linearly with the external force, indicating that the force distribution was uniquely determined by the symmetric architecture of tDCB. In contrast, internal forces due to stiff stilbene resulted in an asymmetric force distribution within tDCB, which indicated a different geometry of force application and supported the important role of linkers in the mechanochemical reactivity of tDCB. In addition, three coordinates were identified through which the distributed forces contributed most to rate acceleration. These coordinates are mostly parallel to the coordinate connecting the two CH3 termini of tDCB. Our results confirm previous observations that the linker outside of the reactive moiety, such as a stretched polymer or a macrocycle, affects its mechanochemical reactivity. We expect FM-FDA to be of wide use to understand and quantitatively predict mechanochemical reactivity, including the challenging cases of systems within strained macrocycles."],["dc.identifier.doi","10.1002/cphc.201300252"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/12158"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Force Distribution Analysis of Mechanochemically Reactive Dimethylcyclobutene"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","557"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Journal of Structural Biology"],["dc.bibliographiccitation.lastpage","569"],["dc.bibliographiccitation.volume","157"],["dc.contributor.author","Gräter, Frauke"],["dc.contributor.editor","Grubmüller, Helmut"],["dc.date.accessioned","2018-04-18T20:02:42Z"],["dc.date.available","2018-04-18T20:02:42Z"],["dc.date.issued","2007"],["dc.description.abstract","Folding experiments of single ubiquitin molecules under force clamp using an atomic force microscope revealed a dynamic long-lived intermediate with nanometer scale end-to-end distance fluctuations along an unexpectedly complex folding pathway. To examine the nature of this intermediate at the atomic level as well as the driving forces that give rise to the observed fluctuations, we performed molecular dynamics refolding simulations of unfolded ubiquitin under constant force. After an initial fast collapse, we find a highly dynamic, broad ensemble of conformations with partial and continuously changing secondary structure and side chain interactions. This ensemble resembles a molten-globule-like state, similar in nature to the previously described non-native state of ubiquitin in solution, but stretched by the external force. The scale of the end-to-end distance fluctuations derived from the simulations compares well with experiment. Transient formation of unspecific and metastable hydrophobic clusters along the chain are found to give rise to the observed end-to-end distance fluctuations. These distinct collapses, interpreted as folding attempts, imply an upper limit for the folding attempt frequency of ∼10 ns. Our results suggest possible relations between force-induced unfolding and temperature or chemically induced denaturation."],["dc.identifier.doi","10.1016/j.jsb.2006.11.005"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13237"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Fluctuations of primary ubiquitin folding intermediates in a force clamp"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13385"],["dc.bibliographiccitation.issue","36"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America"],["dc.bibliographiccitation.lastpage","13390"],["dc.bibliographiccitation.volume","105"],["dc.contributor.author","Puchner, Elias M"],["dc.contributor.author","Alexandrovich, Alexander"],["dc.contributor.author","Kho, Ay Lin"],["dc.contributor.author","Hensen, Ulf"],["dc.contributor.author","Schäfer, Lars V."],["dc.contributor.author","Brandmeier, Birgit"],["dc.contributor.author","Gräter, Frauke"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Gaub, Hermann"],["dc.contributor.author","Gautel, Mathias"],["dc.date.accessioned","2018-02-13T13:12:50Z"],["dc.date.available","2018-02-13T13:12:50Z"],["dc.date.issued","2008-09-09"],["dc.description.abstract","Biological responses to mechanical stress require strain-sensing molecules, whose mechanically induced conformational changes are relayed to signaling cascades mediating changes in cell and tissue properties. In vertebrate muscle, the giant elastic protein titin is involved in strain sensing via its C-terminal kinase domain (TK) at the sarcomeric M-band and contributes to the adaptation of muscle in response to changes in mechanical strain. TK is regulated in a unique dual autoinhibition mechanism by a C-terminal regulatory tail, blocking the ATP binding site, and tyrosine autoinhibition of the catalytic base. For access to the ATP binding site and phosphorylation of the autoinhibitory tyrosine, the C-terminal autoinhibitory tail needs to be removed. Here, we use AFM-based single-molecule force spectroscopy, molecular dynamics simulations, and enzymatics to study the conformational changes during strain-induced activation of human TK. We show that mechanical strain activates ATP binding before unfolding of the structural titin domains, and that TK can thus act as a biological force sensor. Furthermore, we identify the steps in which the autoinhibition of TK is mechanically relieved at low forces, leading to binding of the cosubstrate ATP and priming the enzyme for subsequent autophosphorylation and substrate turnover."],["dc.identifier.doi","10.1073/pnas.0805034105"],["dc.identifier.pmid","18765796"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/12229"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1091-6490"],["dc.relation.haserratum","/handle/2/80234"],["dc.title","Mechanoenzymatics of titin kinase"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","831"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","846"],["dc.bibliographiccitation.volume","127"],["dc.contributor.author","Takamori, Shigeo"],["dc.contributor.author","Holt, Matthew"],["dc.contributor.author","Stenius, Katinka"],["dc.contributor.author","Lemke, Edward A."],["dc.contributor.author","Gronborg, Mads"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Schenck, Stephan"],["dc.contributor.author","Brügger, Britta"],["dc.contributor.author","Ringler, Philippe"],["dc.contributor.author","Müller, Shirley A."],["dc.contributor.author","Rammner, Burkhard"],["dc.contributor.author","Graeter, Frauke"],["dc.contributor.author","Hub, Jochen S."],["dc.contributor.author","Groot, Bert L. de"],["dc.contributor.author","Mieskes, Gottfried"],["dc.contributor.author","Moriyama, Yoshinori"],["dc.contributor.author","Klingauf, Juergen"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Heuser, John"],["dc.contributor.author","Wieland, Felix"],["dc.contributor.author","Jahn, Reinhard"],["dc.date.accessioned","2017-09-07T11:49:54Z"],["dc.date.available","2017-09-07T11:49:54Z"],["dc.date.issued","2006"],["dc.description.abstract","Membrane traffic in eukaryotic cells involves transport of vesicles that bud from a donor compartment and fuse with an acceptor compartment. Common principles of budding and fusion have emerged, and many of the proteins involved in these events are now known. However, a detailed picture of an entire trafficking organelle is not yet available. Using synaptic vesicles as a model, we have now determined the protein and lipid composition; measured vesicle size, density, and mass; calculated the average protein and lipid mass per vesicle; and determined the copy number of more than a dozen major constituents. A model has been constructed that integrates all quantitative data and includes structural models of abundant proteins. Synaptic vesicles are dominated by proteins, possess a surprising diversity of trafficking proteins, and, with the exception of the V-ATPase that is present in only one to two copies, contain numerous copies of proteins essential for membrane traffic and neurotransmitter uptake."],["dc.identifier.doi","10.1016/j.cell.2006.10.030"],["dc.identifier.gro","3143587"],["dc.identifier.isi","000242330600027"],["dc.identifier.pmid","17110340"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1117"],["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","0092-8674"],["dc.title","Molecular anatomy of a trafficking organelle"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","S0022283621006240"],["dc.bibliographiccitation.firstpage","167387"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Molecular Biology"],["dc.bibliographiccitation.volume","434"],["dc.contributor.author","Martin, Isabel M."],["dc.contributor.author","Aponte-Santamaría, Camilo"],["dc.contributor.author","Schmidt, Lisa"],["dc.contributor.author","Hedtfeld, Marius"],["dc.contributor.author","Iusupov, Adel"],["dc.contributor.author","Musacchio, Andrea"],["dc.contributor.author","Gräter, Frauke"],["dc.date.accessioned","2022-05-02T07:46:56Z"],["dc.date.available","2022-05-02T07:46:56Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1016/j.jmb.2021.167387"],["dc.identifier.pii","S0022283621006240"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107170"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.relation.issn","0022-2836"],["dc.title","Phosphorylation tunes elongation propensity and cohesiveness of INCENP’s intrinsically disordered region"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13070"],["dc.bibliographiccitation.issue","37"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","13074"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Andresen, Martin"],["dc.contributor.author","Wahl, Markus C."],["dc.contributor.author","Stiel, André C."],["dc.contributor.author","Gräter, Frauke"],["dc.contributor.author","Schäfer, Lars V."],["dc.contributor.author","Trowitzsch, Simon"],["dc.contributor.author","Weber, Gert"],["dc.contributor.author","Eggeling, Christian"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Jakobs, Stefan"],["dc.date.accessioned","2017-09-07T11:54:19Z"],["dc.date.available","2017-09-07T11:54:19Z"],["dc.date.issued","2005"],["dc.description.abstract","Proteins that can be reversibly photoswitched between a fluorescent and a nonfluorescent state bear enormous potential in diverse fields, such as data storage, in vivo protein tracking, and subdiffraction resolution light microscopy. However, these proteins could hitherto not live up to their full potential because the molecular switching mechanism is not resolved. Here, we clarify the molecular photoswitching mechanism of asFP595, a green fluorescent protein (GFP)-like protein that can be transferred from a nonfluorescent \"off\" to a fluorescent \"on\" state and back again, by green and blue light, respectively. To this end, we establish reversible photoswitching of fluorescence in whole protein crystals and show that the switching kinetics in the crystal is identical with that in solution. Subsequent x-ray analysis demonstrated that upon the absorption of a green photon, the chromophore isomerizes from a trans (off) to a cis (on) state. Molecular dynamics calculations suggest that isomerization occurs through a bottom hula twist mechanism with concomitant rotation of both bonds of the chromophoric methine ring bridge. This insight into the switching mechanism should facilitate the targeted design of photo-switchable proteins. Reversible photoswitching of the protein chromophore system within intact crystals also constitutes a step toward the use of fluorescent proteins in three-dimensional data recording."],["dc.identifier.doi","10.1073/pnas.0502772102"],["dc.identifier.gro","3143804"],["dc.identifier.isi","000231916300014"],["dc.identifier.pmid","16135569"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1359"],["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","Structure and mechanism of the reversible photoswitch of a fluorescent protein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","790"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophys J."],["dc.bibliographiccitation.lastpage","804"],["dc.bibliographiccitation.volume","88"],["dc.contributor.author","Gräter, Frauke"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Jiang, Hualiang"],["dc.contributor.author","Shen, Jianhua"],["dc.contributor.author","Gautel, Mathias"],["dc.date.accessioned","2018-04-23T08:56:22Z"],["dc.date.available","2018-04-23T08:56:22Z"],["dc.date.issued","2005"],["dc.description.abstract","The conversion of mechanical stress into a biochemical signal in a muscle cell requires a force sensor. Titin kinase, the catalytic domain of the elastic muscle protein titin, has been suggested as a candidate. Its activation requires major conformational changes resulting in the exposure of its active site. Here, force-probe molecular dynamics simulations were used to obtain insight into the tension-induced activation mechanism. We find evidence for a sequential mechanically induced opening of the catalytic site without complete domain unfolding. Our results suggest the rupture of two terminal β-sheets as the primary unfolding steps. The low force resistance of the C-terminal relative to the N-terminal β-sheet is attributed to their different geometry. A subsequent rearrangement of the autoinhibitory tail is seen to lead to the exposure of the active site, as is required for titin kinase activity. These results support the hypothesis of titin kinase as a force sensor."],["dc.identifier.doi","10.1529/biophysj.104.052423"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13256"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Mechanically Induced Titin Kinase Activation Studied by Force-Probe Molecular Dynamics Simulations"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1567"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Structure"],["dc.bibliographiccitation.lastpage","1576"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Graeter, Frauke"],["dc.contributor.author","de Groot, Bert L."],["dc.contributor.author","Jiang, Hualiang"],["dc.contributor.author","Grubmüller, Helmut"],["dc.date.accessioned","2017-09-07T11:52:32Z"],["dc.date.available","2017-09-07T11:52:32Z"],["dc.date.issued","2006"],["dc.description.abstract","Pheromone-binding proteins (PBP) supply olfactory neuron cells with pheromones by binding the ligands they are tailored for and carrying them to their receptor. The function of a PBP as an efficient carrier requires fast ligand uptake and release. The molecular basis of the ligand-binding mechanism was addressed here for the intriguing case of the PBP of the silk moth Bombyx mori. This PBP completely encapsulates its ligand bombykol without displaying any obvious ligand entrance/exit sites. Here, two opposite dissociation routes were identified as the most likely entrance/exit paths by replica-exchange molecular dynamics, essential dynamics, and force-probe molecular dynamics simulations. One of the paths runs along a flexible front lid; the other along the termini at the back. Calculated forces and energies suggest that both routes are physiologically relevant. The multiplicity of pathways may reduce or tune the entropic barrier for ligand binding."],["dc.identifier.doi","10.1016/j.str.2006.08.012"],["dc.identifier.gro","3143621"],["dc.identifier.isi","000241241800010"],["dc.identifier.pmid","17027505"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1155"],["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","0969-2126"],["dc.title","Ligand-release pathways in the pheromone-binding protein of Bombyx mori"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1577"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Structure"],["dc.bibliographiccitation.lastpage","1586"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Gräter, F."],["dc.contributor.author","Xu, W."],["dc.contributor.author","Leal, W."],["dc.contributor.author","Grubmüller, H."],["dc.date.accessioned","2018-04-19T08:04:55Z"],["dc.date.available","2018-04-19T08:04:55Z"],["dc.date.issued","2006"],["dc.description.abstract","Pheromone-binding proteins are postulated to contribute to the exquisite specificity of the insect's olfactory system, acting as a filter by preferentially binding only one of the components of the natural pheromone. Here, we investigated the possible discrimination of the two very similar components of the natural pheromone gland from the silk moth, Bombyx mori, bombykol and bombykal, by the only pheromone-binding protein (BmorPBP) known to be expressed in the pheromone-detecting sensilla. Free-energy calculations and virtual docking indicate that both bombykol and bombykal bind to BmorPBP with similar affinity. In addition, in vitro competitive binding assays showed that both bombykol and bombykal were bound by BmorPBP with nearly the same high affinity. While BmorPBP might filter out other physiologically irrelevant compounds hitting the sensillar lymph, discrimination between the natural pheromone compounds must be achieved by molecular interactions with their cognate receptors."],["dc.identifier.doi","10.1016/j.str.2006.08.013"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13244"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Pheromone Discrimination by the Pheromone-Binding Protein of Bombyx mori"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","MPIbpc news"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Andresen, Martin"],["dc.contributor.author","Jakobs, Stefan"],["dc.contributor.author","Wahl, Markus C."],["dc.contributor.author","Hell, Stefan W."],["dc.contributor.author","Stiel, André C."],["dc.contributor.author","Gräter, Frauke"],["dc.contributor.author","Trowitzsch, Simon"],["dc.contributor.author","Schäfer, Lars V."],["dc.contributor.author","Eggeling, Christian"],["dc.contributor.author","Weber, Gert"],["dc.contributor.author","Grubmüller, Helmut"],["dc.date.accessioned","2018-04-23T08:45:37Z"],["dc.date.available","2018-04-23T08:45:37Z"],["dc.date.issued","2005"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13255"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.title","Insight into the structure and mechanism of the reversible photoswitch of a fluorescent protein: A multi-departmental research approach"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]