Jovin, Thomas M.

[["dc.bibliographiccitation.firstpage","1430"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","1435"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Bertoncini, Carlos W."],["dc.contributor.author","Jung, Y. S."],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Hoyer, W."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:43:01Z"],["dc.date.available","2017-09-07T11:43:01Z"],["dc.date.issued","2005"],["dc.description.abstract","In idiopathic Parkinson's disease, intracytoplasmic neuronal inclusions (Lewy bodies) containing aggregates of the protein a-synuclein (alphaS) are deposited in the pigmented nuclei of the brainstem. The mechanisms underlying the structural transition of innocuous, presumably natively unfolded, aS to neurotoxic forms are largely unknown. Using paramagnetic relaxation enhancement and NMR dipolar couplings, we show that monomeric aS assumes conformations that are stabilized by long-range interactions and act to inhibit oligomerization and aggregation. The autoinhibitory conformations fluctuate in the range of nanoseconds to microseconds corresponding to the time scale of secondary structure formation during folding. Polyamine binding and/or temperature increase, conditions that induce aggregation in vitro, release this inherent tertiary structure, leading to a completely unfolded conformation that associates readily. Stabilization of the native, autoinhibitory structure of alphaS constitutes a potential strategy for reducing or inhibiting oligomerization and aggregation in Parkinson's disease."],["dc.identifier.doi","10.1073/pnas.0407146102"],["dc.identifier.gro","3143902"],["dc.identifier.isi","000226877300034"],["dc.identifier.pmid","15671169"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1467"],["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","Release of long-range tertiary interactions potentiates aggregation of natively unstructured alpha-synuclein"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","L1"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.lastpage","L3"],["dc.bibliographiccitation.volume","101"],["dc.contributor.author","Karyagina, Irina"],["dc.contributor.author","Becker, Stefan"],["dc.contributor.author","Giller, Karin"],["dc.contributor.author","Riedel, Dietmar"],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Bennati, Marina"],["dc.date.accessioned","2017-09-07T11:44:06Z"],["dc.date.available","2017-09-07T11:44:06Z"],["dc.date.issued","2011"],["dc.description.abstract","The misfolding of alpha-synuclein (alpha S) to a cross-beta-sheet amyloid structure is associated with pathological conditions in Parkinson's and other neurodegenerative diseases. Using pulse electron paramagnetic resonance spectroscopy combined with a cross-labeling strategy involving four double mutants, we were able to determine the intramolecular distance between the extremal beta-strands. The distance of 4.5 +/- 0.5 nm is in good agreement with the dimensions of a protofilament reported by other low-resolution techniques, such as x-ray scattering and atomic force microscopy."],["dc.identifier.doi","10.1016/j.bpj.2011.05.052"],["dc.identifier.gro","3142700"],["dc.identifier.isi","000292571700001"],["dc.identifier.pmid","21723808"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/133"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: Max Planck Society"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0006-3495"],["dc.title","Electron Paramagnetic Resonance Spectroscopy Measures the Distance between the External beta-Strands of Folded alpha-Synuclein in Amyloid Fibrils"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","JA0618649"],["dc.bibliographiccitation.firstpage","9893"],["dc.bibliographiccitation.issue","30"],["dc.bibliographiccitation.journal","Journal of the American Chemical Society"],["dc.bibliographiccitation.lastpage","9901"],["dc.bibliographiccitation.volume","128"],["dc.contributor.author","Binolfi, Andres"],["dc.contributor.author","Rasia, Rodolfo M."],["dc.contributor.author","Bertoncini, Carlos W."],["dc.contributor.author","Ceolin, Marcelo"],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Fernandez, Claudio O."],["dc.date.accessioned","2017-09-07T11:52:36Z"],["dc.date.available","2017-09-07T11:52:36Z"],["dc.date.issued","2006"],["dc.description.abstract","The aggregation of alpha-synuclein (AS) is characteristic of Parkinson's disease and other neurodegenerative synucleinopathies. Interactions with metal ions affect dramatically the kinetics of fibrillation of AS in vitro and are proposed to play a potential role in vivo. We recently showed that Cu(II) binds at the N-terminus of AS with high affinity (K(d) similar to 0.1 mu M) and accelerates its fibrillation. In this work we investigated the binding features of the divalent metal ions Fe(II), Mn(II), Co(II), and Ni(II), and their effects on AS aggregation. By exploiting the different paramagnetic properties of these metal ions, NMR spectroscopy provides detailed information about the protein-metal interactions at the atomic level. The divalent metal ions bind preferentially and with low affinity (millimolar) to the C-terminus of AS, the primary binding site being the (119)DPDNEA(124) motif, in which Asp121 acts as the main anchoring residue. Combined with backbone residual dipolar coupling measurements, these results suggest that metal binding is not driven exclusively by electrostatic interactions but is mostly determined by the residual structure of the C-terminus of AS. A comparative analysis with Cu(II) revealed a hierarchal effect of AS-metal(II) interactions on AS aggregation kinetics, dictated by structural factors corresponding to different protein domains. These findings reveal a strong link between the specificity of AS-metal(II) interactions and the enhancement of aggregation of AS in vitro. The elucidation of the structural basis of AS metal binding specificity is then required to elucidate the mechanism and clarify the role of metal-protein interactions in the etiology of Parkinson's disease."],["dc.identifier.doi","10.1021/ja0618649"],["dc.identifier.gro","3143646"],["dc.identifier.isi","000239278600069"],["dc.identifier.pmid","16866548"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1183"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0002-7863"],["dc.title","Interaction of alpha-synuclein with divalent metal ions reveals key differences: A link between structure, binding specificity and fibrillation enhancement"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2039"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","EMBO Journal"],["dc.bibliographiccitation.lastpage","2046"],["dc.bibliographiccitation.volume","23"],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Hoyer, W."],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Jares-Erijman, E. A."],["dc.contributor.author","Subramaniam, V."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Jovin, Thomas M."],["dc.date.accessioned","2017-09-07T11:43:22Z"],["dc.date.available","2017-09-07T11:43:22Z"],["dc.date.issued","2004"],["dc.description.abstract","The aggregation of alpha-synuclein is characteristic of Parkinson's disease (PD) and other neurodegenerative synucleinopathies. The 140-aa protein is natively unstructured; thus, ligands binding to the monomeric form are of therapeutic interest. Biogenic polyamines promote the aggregation of alpha-synuclein and may constitute endogenous agents modulating the pathogenesis of PD. We characterized the complexes of natural and synthetic polyamines with alpha-synuclein by NMR and assigned the binding site to C-terminal residues 109-140. Dissociation constants were derived from chemical shift perturbations. Greater polyamine charge (+2 --> +5) correlated with increased affinity and enhancement of fibrillation, for which we propose a simple kinetic mechanism involving a dimeric nucleation center. According to the analysis, polyamines increase the extent of nucleation by similar to10(4) and the rate of monomer addition similar to40-fold. Significant secondary structure is not induced in monomeric alpha-synuclein by polyamines at 15degreesC. Instead, NMR reveals changes in a region (aa 22-93) far removed from the polyamine binding site and presumed to adopt the beta-sheet conformation characteristic of fibrillar alpha-synuclein. We conclude that the C-terminal domain acts as a regulator of alpha-synuclein aggregation."],["dc.identifier.doi","10.1038/sj.emboj.7600211"],["dc.identifier.gro","3143987"],["dc.identifier.isi","000221499800003"],["dc.identifier.pmid","15103328"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1561"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0261-4189"],["dc.title","NMR of alpha-synuclein-polyamine complexes elucidates the mechanism and kinetics of induced aggregation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","396A"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.lastpage","396A"],["dc.bibliographiccitation.volume","88"],["dc.contributor.author","Bertoncini, C. W."],["dc.contributor.author","Cherny, D. I."],["dc.contributor.author","Fernandez, C. O."],["dc.contributor.author","Garfinkel, E."],["dc.contributor.author","Griesinger, C."],["dc.contributor.author","Hoyer, W."],["dc.contributor.author","Jares-Erijman, E. A."],["dc.contributor.author","Jovin, T. M."],["dc.contributor.author","Marsh, D."],["dc.contributor.author","Rasia, R. M."],["dc.contributor.author","Roberti, M. J."],["dc.contributor.author","Subramaniam, V."],["dc.contributor.author","Zweckstetter, M."],["dc.date.accessioned","2017-09-07T11:45:12Z"],["dc.date.available","2017-09-07T11:45:12Z"],["dc.date.issued","2005"],["dc.identifier.gro","3145513"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/3222"],["dc.notes.intern","lifescience"],["dc.notes.status","public"],["dc.notes.submitter","chake"],["dc.relation.eventstart","2005"],["dc.relation.issn","0006-3495"],["dc.title","3D structure, ligand binding, autoinhibition, aggregation, and cellular distribution of wild-type, mutant, and labeled alpha-synuclein"],["dc.type","conference_paper"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4294"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","4299"],["dc.bibliographiccitation.volume","102"],["dc.contributor.author","Rasia, Rodolfo M."],["dc.contributor.author","Bertoncini, Carlos W."],["dc.contributor.author","Marsh, D."],["dc.contributor.author","Hoyer, W."],["dc.contributor.author","Cherny, D. I."],["dc.contributor.author","Zweckstetter, Markus"],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Fernandez, Claudio O."],["dc.date.accessioned","2017-09-07T11:54:30Z"],["dc.date.available","2017-09-07T11:54:30Z"],["dc.date.issued","2005"],["dc.description.abstract","The aggregation of alpha-synuclein (AS) is characteristic of Parkinson's disease and other neurodegenerative synucleinopathies. We demonstrate here that Cu(II) ions are effective in accelerating AS aggregation at physiologically relevant concentrations without altering the resultant fibrillar structures. By using numerous spectroscopic techniques (absorption, CD, EPR, and NMR), we have located the primary binding for Cu(II) to a specific site in the N terminus, involving His-50 as the anchoring residue and other nitrogen/oxygen donor atoms in a square planar or distorted tetragonal geometry. The carboxylate-rich C terminus, originally thought to drive copper binding, is able to coordinate a second Cu(II) equivalent, albeit with a 300-fold reduced affinity. The NMR analysis of AS-Cu(II) complexes reveals the existence of conformational restrictions in the native state of the protein. The metallobiology of Cu(II) in Parkinson's disease is discussed by a comparative analysis with other Cu(II)-binding proteins involved in neurodegenerative disorders."],["dc.identifier.doi","10.1073/pnas.0407881102"],["dc.identifier.gro","3143880"],["dc.identifier.isi","000227854800015"],["dc.identifier.pmid","15767574"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1442"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0027-8424"],["dc.title","Structural characterization of copper(II) binding to alpha-synuclein: Insights into the bioinorganic chemistry of Parkinson's disease"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","30649"],["dc.bibliographiccitation.issue","35"],["dc.bibliographiccitation.journal","Journal of biological chemistry"],["dc.bibliographiccitation.lastpage","30652"],["dc.bibliographiccitation.volume","280"],["dc.contributor.author","Bertoncini, Carlos W."],["dc.contributor.author","Fernandez, Claudio O."],["dc.contributor.author","Griesinger, Christian"],["dc.contributor.author","Jovin, Thomas M."],["dc.contributor.author","Zweckstetter, Markus"],["dc.date.accessioned","2017-09-07T11:54:19Z"],["dc.date.available","2017-09-07T11:54:19Z"],["dc.date.issued","2005"],["dc.description.abstract","A30P and A53T mutations of the presynaptic protein alpha- synuclein are associated with familial forms of Parkinson disease. NMR spectroscopy demonstrates that Parkinsonism- linked mutations greatly perturb specific tertiary interactions essential for the native state of alpha- synuclein. However, alpha- synuclein is not completely unfolded but exhibits structural fluctuations on the time scale of secondary structure formation and loses its native conformation gradually when protein stability decreases. The redistribution of the ensemble of alpha- synuclein conformers may underlie toxic gain- of- function by fostering self- association and altered binding affinity to ligands and receptors."],["dc.identifier.doi","10.1074/jbc.C500288200"],["dc.identifier.gro","3143805"],["dc.identifier.isi","000231487800002"],["dc.identifier.pmid","16020550"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1360"],["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.issn","0021-9258"],["dc.title","Familial mutants of alpha-synuclein with increased neurotoxicity have a destabilized conformation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]