Griesinger, Christian

[["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.firstpage","12404"],["dc.bibliographiccitation.issue","82"],["dc.bibliographiccitation.journal","Chemical Communications"],["dc.bibliographiccitation.lastpage","12407"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Rezaei-Ghaleh, Nasrollah"],["dc.contributor.author","Munari, Francesca"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Assfalg, Michael"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2020-12-10T18:11:26Z"],["dc.date.available","2020-12-10T18:11:26Z"],["dc.date.issued","2019"],["dc.description.abstract","This NMR probe of water dynamics enables viscosity determination in concentrated and crowded solutions and allows quantifying internal fluidity within biological condensates."],["dc.description.abstract","We present an NMR method based on natural abundance 17 O relaxation of water to determine effective viscosity in biological aqueous samples. The method accurately captures viscosity of dilute and crowded protein solutions and offers a fairly simple way to quantify the internal fluidity of biological condensates formed through phase separation."],["dc.description.abstract","This NMR probe of water dynamics enables viscosity determination in concentrated and crowded solutions and allows quantifying internal fluidity within biological condensates."],["dc.description.abstract","We present an NMR method based on natural abundance 17 O relaxation of water to determine effective viscosity in biological aqueous samples. The method accurately captures viscosity of dilute and crowded protein solutions and offers a fairly simple way to quantify the internal fluidity of biological condensates formed through phase separation."],["dc.identifier.doi","10.1039/C9CC06124J"],["dc.identifier.eissn","1364-548X"],["dc.identifier.issn","1359-7345"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16666"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/74010"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.relation.eissn","1364-548X"],["dc.relation.issn","1359-7345"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A facile oxygen-17 NMR method to determine effective viscosity in dilute, molecularly crowded and confined aqueous media"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","109"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","The European Physical Journal E - Soft Matter"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Jain, R."],["dc.contributor.author","Petri, M."],["dc.contributor.author","Kirschbaum, S."],["dc.contributor.author","Feindt, H."],["dc.contributor.author","Steltenkamp, Siegfried"],["dc.contributor.author","Sonnenkalb, S."],["dc.contributor.author","Becker, S."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Menzel, A."],["dc.contributor.author","Burg, T. P."],["dc.contributor.author","Techert, S."],["dc.date.accessioned","2017-09-07T11:47:08Z"],["dc.date.available","2017-09-07T11:47:08Z"],["dc.date.issued","2013"],["dc.description.abstract","Small-angle X-ray scattering provides global, shape-sensitive structural information about macromolecules in solution. Its extension to time dimension in the form of time-resolved SAXS investigations and combination with other time-resolved biophysical methods contributes immensely to the study of protein dynamics. TR-SAXS can also provide unique information about the global structures of transient intermediates during protein dynamics. An experimental set-up with low protein consumption is essential for an extensive use of TR-SAXS experiments on protein dynamics. In this direction, a newly developed 20-microchannel microfluidic continuous-flow mixer was combined with SAXS. With this set-up, we demonstrate ubiquitin unfolding dynamics after rapid mixing with the chaotropic agent Guanidinium-HCl within milliseconds using only similar to 40 nanoliters of the protein sample per scattering image. It is suggested that, in the future, this new TR-SAXS platform will help to increase the use of time-resolved small-angle X-ray scattering, wide-angle X-ray scattering and neutron scattering experiments for studying protein dynamics in the early millisecond regime. The potential research field for this set-up includes protein folding, protein misfolding, aggregation in amyloidogenic diseases, function of intrinsically disordered proteins and various protein-ligand interactions."],["dc.identifier.doi","10.1140/epje/i2013-13109-9"],["dc.identifier.gro","3142281"],["dc.identifier.isi","000325224100001"],["dc.identifier.pmid","24092048"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6542"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Nanoscale Photon Imaging of the DFG [SFB 755]"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1292-8941"],["dc.relation.orgunit","Institut für Röntgenphysik"],["dc.relation.workinggroup","RG Techert (Structural Dynamics in Chemical Systems)"],["dc.title","X-ray scattering experiments with high-flux X-ray source coupled rapid mixing microchannel device and their potential for high-flux neutron scattering investigations"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","23"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Journal of Biomolecular NMR"],["dc.bibliographiccitation.lastpage","44"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Farès, Christophe"],["dc.contributor.author","Lakomek, Nils-Alexander"],["dc.contributor.author","Walter, Korvin F. A."],["dc.contributor.author","Frank, Benedikt T. C."],["dc.contributor.author","Meiler, Jens"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2017-09-07T11:46:50Z"],["dc.date.available","2017-09-07T11:46:50Z"],["dc.date.issued","2009"],["dc.description.abstract","This study presents the first application of the model-free analysis (MFA) (Meiler in J Am Chem Soc 123:6098-6107, 2001; Lakomek in J Biomol NMR 34:101-115, 2006) to methyl group RDCs measured in 13 different alignment media in order to describe their supra-tau (c) dynamics in ubiquitin. Our results indicate that methyl groups vary from rigid to very mobile with good correlation to residue type, distance to backbone and solvent exposure, and that considerable additional dynamics are effective at rates slower than the correlation time tau (c). In fact, the average amplitude of motion expressed in terms of order parameters S (2) associated with the supra-tau (c) window brings evidence to the existence of fluctuations contributing as much additional mobility as those already present in the faster ps-ns time scale measured from relaxation data. Comparison to previous results on ubiquitin demonstrates that the RDC-derived order parameters are dominated both by rotameric interconversions and faster libration-type motions around equilibrium positions. They match best with those derived from a combined J-coupling and residual dipolar coupling approach (Chou in J Am Chem Soc 125:8959-8966, 2003) taking backbone motion into account. In order to appreciate the dynamic scale of side chains over the entire protein, the methyl group order parameters are compared to existing dynamic ensembles of ubiquitin. Of those recently published, the broadest one, namely the EROS ensemble (Lange in Science 320:1471-1475, 2008), fits the collection of methyl group order parameters presented here best. Last, we used the MFA-derived averaged spherical harmonics to perform highly-parameterized rotameric searches of the side chains conformation and find expanded rotamer distributions with excellent fit to our data. These rotamer distributions suggest the presence of concerted motions along the side chains."],["dc.identifier.doi","10.1007/s10858-009-9354-7"],["dc.identifier.gro","3143062"],["dc.identifier.isi","000269079100005"],["dc.identifier.pmid","19652920"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/534"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0925-2738"],["dc.title","Accessing ns-mu s side chain dynamics in ubiquitin with methyl RDCs"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3115"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences of the United States of America : PNAS"],["dc.bibliographiccitation.lastpage","3120"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Salvi, Michele"],["dc.contributor.author","Schomburg, Benjamin"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Graf, Sabrina"],["dc.contributor.author","Unden, Gottfried"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Lange, Adam"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2018-01-17T11:33:34Z"],["dc.date.available","2018-01-17T11:33:34Z"],["dc.date.issued","2017"],["dc.description.abstract","Bacteria use membrane-integral sensor histidine kinases (HK) to perceive stimuli and transduce signals from the environment to the cytosol. Information on how the signal is transmitted across the membrane by HKs is still scarce. Combining both liquid- and solid-state NMR, we demonstrate that structural rearrangements in the extracytoplasmic, citrate-sensing Per-Arnt-Sim (PAS) domain of HK CitA are identical for the isolated domain in solution and in a longer construct containing the membrane-embedded HK and lacking only the kinase core. We show that upon citrate binding, the PAS domain contracts, resulting in a shortening of the C-terminal β-strand. We demonstrate that this contraction of the PAS domain, which is well characterized for the isolated domain, is the signal transmitted to the transmembrane (TM) helices in a CitA construct in liposomes. Putting the extracytoplasmic PAS domain into context of the membrane-embedded CitA construct slows down citrate-binding kinetics by at least a factor of 60, confirming that TM helix motions are linked to the citrate-binding event. Our results are confirmation of a hallmark of the HK signal transduction mechanism with atomic resolution on a full-length construct lacking only the kinase core domain."],["dc.identifier.doi","10.1073/pnas.1620286114"],["dc.identifier.pmid","28265100"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/11680"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1091-6490"],["dc.title","Sensory domain contraction in histidine kinase CitA triggers transmembrane signaling in the membrane-bound sensor"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","eabg2174"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","Science Advances"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Antonschmidt, Leif"],["dc.contributor.author","Dervişoğlu, Rıza"],["dc.contributor.author","Sant, Vrinda"],["dc.contributor.author","Tekwani Movellan, Kumar"],["dc.contributor.author","Mey, Ingo P."],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Steinem, Claudia"],["dc.contributor.author","Becker, Stefan T."],["dc.contributor.author","Andreas, Loren B."],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2021-06-01T09:42:06Z"],["dc.date.available","2021-06-01T09:42:06Z"],["dc.date.issued","2021"],["dc.description.abstract","Recent advances in the structural biology of disease-relevant α-synuclein fibrils have revealed a variety of structures, yet little is known about the process of fibril aggregate formation. Characterization of intermediate species that form during aggregation is crucial; however, this has proven very challenging because of their transient nature, heterogeneity, and low population. Here, we investigate the aggregation of α-synuclein bound to negatively charged phospholipid small unilamellar vesicles. Through a combination of kinetic and structural studies, we identify key time points in the aggregation process that enable targeted isolation of prefibrillar and early fibrillar intermediates. By using solid-state nuclear magnetic resonance, we show the gradual buildup of structural features in an α-synuclein fibril filament, revealing a segmental folding process. We identify distinct membrane-binding domains in α-synuclein aggregates, and the combined data are used to present a comprehensive mechanism of the folding of α-synuclein on lipid membranes."],["dc.identifier.doi","10.1126/sciadv.abg2174"],["dc.identifier.pmid","33990334"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85143"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/259"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","2375-2548"],["dc.relation.workinggroup","RG Griesinger"],["dc.relation.workinggroup","RG Steinem (Biomolecular Chemistry)"],["dc.rights","CC BY-NC 4.0"],["dc.title","Insights into the molecular mechanism of amyloid filament formation: Segmental folding of α-synuclein on lipid membranes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","8971"],["dc.bibliographiccitation.issue","47"],["dc.bibliographiccitation.journal","Angewandte Chemie International Edition"],["dc.bibliographiccitation.lastpage","8974"],["dc.bibliographiccitation.volume","49"],["dc.contributor.author","Himmel, Sebastian"],["dc.contributor.author","Wolff, Sebastian"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Lee, Donghan"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2017-09-07T11:46:11Z"],["dc.date.available","2017-09-07T11:46:11Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1002/anie.201003965"],["dc.identifier.gro","3142990"],["dc.identifier.isi","000284708400014"],["dc.identifier.pmid","20939030"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/454"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Max-Planck Gesellschaft"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Wiley-v C H Verlag Gmbh"],["dc.relation.issn","1433-7851"],["dc.title","Detection and Identification of Protein-Phosphorylation Sites in Histidines through HNP Correlation Patterns"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","27731"],["dc.bibliographiccitation.issue","33"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","27742"],["dc.bibliographiccitation.volume","287"],["dc.contributor.author","Himmel, Sebastian"],["dc.contributor.author","Zschiedrich, Christopher P."],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Hsiao, He-Hsuan"],["dc.contributor.author","Wolff, Sebastian"],["dc.contributor.author","Diethmaier, Christine"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Lee, Donghan"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Stuelke, Joerg"],["dc.date.accessioned","2017-09-07T11:48:29Z"],["dc.date.available","2017-09-07T11:48:29Z"],["dc.date.issued","2012"],["dc.description.abstract","The control of several catabolic operons in bacteria by transcription antitermination is mediated by RNA-binding proteins that consist of an RNA-binding domain and two reiterated phosphotransferase system regulation domains (PRDs). The Bacillus subtilis GlcT antitermination protein regulates the expression of the ptsG gene, encoding the glucose-specific enzyme II of the phosphotransferase system. In the absence of glucose, GlcT becomes inactivated by enzyme II-dependent phosphorylation at its PRD1, whereas the phosphotransferase HPr phosphorylates PRD2. However, here we demonstrate by NMR analysis and mass spectrometry that HPr also phosphorylates PRD1 in vitro but with low efficiency. Size exclusion chromatography revealed that non-phosphorylated PRD1 forms dimers that dissociate upon phosphorylation. The effect of HPr on PRD1 was also investigated in vivo. For this purpose, we used GlcT variants with altered domain arrangements or domain deletions. Our results demonstrate that HPr can target PRD1 when this domain is placed at the C terminus of the protein. In agreement with the in vitro data, HPr exerts a negative control on PRD1. This work provides the first insights into how specificity is achieved in a regulator that contains duplicated regulatory domains with distinct dimerization properties that are controlled by phosphorylation by different phosphate donors. Moreover, the results suggest that the domain arrangement of the PRD-containing antitermination proteins is under selective pressure to ensure the proper regulatory output, i.e. transcription antitermination of the target genes specifically in the presence of the corresponding sugar."],["dc.identifier.doi","10.1074/jbc.M112.388850"],["dc.identifier.gro","3142483"],["dc.identifier.isi","000307840700047"],["dc.identifier.pmid","22722928"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8785"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.title","Determinants of Interaction Specificity of the Bacillus subtilis GlcT Antitermination Protein FUNCTIONALITY AND PHOSPHORYLATION SPECIFICITY DEPEND ON THE ARRANGEMENT OF THE REGULATORY DOMAINS"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1433"],["dc.bibliographiccitation.journal","Biochemical Society transactions"],["dc.bibliographiccitation.lastpage","1437"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Lakomek, Nils-Alexander"],["dc.contributor.author","Lange, Oliver F."],["dc.contributor.author","Walter, Korvin F. A."],["dc.contributor.author","Farès, Christophe"],["dc.contributor.author","Egger, Dalia"],["dc.contributor.author","Lunkenheimer, Peter"],["dc.contributor.author","Meiler, Jens"],["dc.contributor.author","Grubmüller, Helmut"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Groot, Bert L. de"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2017-09-07T11:48:08Z"],["dc.date.available","2017-09-07T11:48:08Z"],["dc.date.issued","2008"],["dc.description.abstract","RDCs (residual dipolar couplings) in NMR spectroscopy provide information about protein dynamics complementary to NMR relaxation methods, especially in the previously inaccessible time window between the protein correlation time tau(c), and 50 mu s. For ubiquitin, new modes of motion of the protein backbone could be detected using RDC-based techniques. An ensemble of ubiquitin based on these RDC values is found to comprise all different conformations that ubiquitin adopts upon binding to different recognition proteins. These conformations in protein-protein complexes had been derived from 46 X-ray structures. Thus, for ubiquitin recognition by other proteins, conformational selection rather than induced fit seems to be the dominant mechanism."],["dc.identifier.doi","10.1042/BST0361433"],["dc.identifier.gro","3143198"],["dc.identifier.isi","000261749200066"],["dc.identifier.pmid","19021570"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/686"],["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","0300-5127"],["dc.title","Residual dipolar couplings as a tool to study molecular recognition of ubiquitin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","680"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","691"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Rodriguez-Castaneda, Fernando"],["dc.contributor.author","Maestre-Martinez, Mitcheell"],["dc.contributor.author","Coudevylle, Nicolas"],["dc.contributor.author","Dimova, Kalina"],["dc.contributor.author","Junge, Harald J."],["dc.contributor.author","Lipstein, Noa"],["dc.contributor.author","Lee, Donghan"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Brose, Nils"],["dc.contributor.author","Jahn, Olaf"],["dc.contributor.author","Carlomagno, Teresa"],["dc.contributor.author","Griesinger, Christian"],["dc.date.accessioned","2017-09-07T11:46:08Z"],["dc.date.available","2017-09-07T11:46:08Z"],["dc.date.issued","2010"],["dc.description.abstract","Ca²⁺ signalling in neurons through calmodulin (CaM) has a prominent function in regulating synaptic vesicle trafficking, transport, and fusion. Importantly, Ca²⁺–CaM binds a conserved region in the priming proteins Munc13‐1 and ubMunc13‐2 and thus regulates synaptic neurotransmitter release in neurons in response to residual Ca2+ signals. We solved the structure of Ca²⁺₄–CaM in complex with the CaM‐binding domain of Munc13‐1, which features a novel 1‐5‐8‐26 CaM‐binding motif with two separated mobile structural modules, each involving a CaM domain. Photoaffinity labelling data reveal the same modular architecture in the complex with the ubMunc13‐2 isoform. The N‐module can be dissociated with EGTA to form the half‐loaded Munc13/Ca²⁺₂–CaM complex. The Ca²⁺ regulation of these Munc13 isoforms can therefore be explained by the modular nature of the Munc13/Ca²⁺–CaM interactions, where the C‐module provides a high‐affinity interaction activated at nanomolar [Ca²⁺]i, whereas the N‐module acts as a sensor at micromolar [Ca²⁺]i. This Ca²⁺/CaM‐binding mode of Munc13 likely constitutes a key molecular correlate of the characteristic Ca²⁺‐dependent modulation of short‐term synaptic plasticity."],["dc.identifier.doi","10.1038/emboj.2009.373"],["dc.identifier.gro","3142967"],["dc.identifier.isi","000274233400015"],["dc.identifier.pmid","20010694"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/429"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Max-Planck Society; Fonds der Chemischen Industrie"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","0261-4189"],["dc.title","Modular architecture of Munc13/calmodulin complexes: dual regulation by Ca²⁺ and possible function in short-term synaptic plasticity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]