@article{14835, abstract = {Aromatische Seitenketten sind wichtige Indikatoren für die Plastizität von Proteinen und bilden oft entscheidende Kontakte bei Protein‐Protein‐Wechselwirkungen. Wir untersuchten aromatische Reste in den beiden strukturell homologen cross‐β Amyloidfibrillen HET‐s und HELLF mit Hilfe eines spezifischen Ansatzes zur Isotopenmarkierung und Festkörper NMR mit Drehung am magischen Winkel. Das dynamische Verhalten der aromatischen Reste Phe und Tyr deutet darauf hin, dass der hydrophobe Amyloidkern starr ist und keine Anzeichen von “atmenden Bewegungen” auf einer Zeitskala von Hunderten von Millisekunden zeigt. Aromatische Reste, die exponiert an der Fibrillenoberfläche sitzen, haben zwar eine starre Ringachse, weisen aber Ringflips auf verschiedenen Zeitskalen von Nanosekunden bis Mikrosekunden auf. Unser Ansatz bietet einen direkten Einblick in die Bewegungen des hydrophoben Kerns und ermöglicht eine bessere Bewertung der Konformationsheterogenität, die aus einem NMR‐Strukturensemble einer solchen Cross‐β‐Amyloidstruktur hervorgeht.}, author = {Becker, Lea Marie and Berbon, Mélanie and Vallet, Alicia and Grelard, Axelle and Morvan, Estelle and Bardiaux, Benjamin and Lichtenecker, Roman and Ernst, Matthias and Loquet, Antoine and Schanda, Paul}, issn = {1521-3757}, journal = {Angewandte Chemie}, keywords = {General Medicine}, number = {19}, publisher = {Wiley}, title = {{Der starre Kern und die flexible Oberfläche von Amyloidfibrillen – Magic‐Angle‐Spinning NMR Spektroskopie von aromatischen Resten}}, doi = {10.1002/ange.202219314}, volume = {135}, year = {2023}, } @misc{14861, abstract = {Cover Page}, author = {Becker, Lea Marie and Berbon, Mélanie and Vallet, Alicia and Grelard, Axelle and Morvan, Estelle and Bardiaux, Benjamin and Lichtenecker, Roman and Ernst, Matthias and Loquet, Antoine and Schanda, Paul}, booktitle = {Angewandte Chemie International Edition}, issn = {1521-3773}, keywords = {General Chemistry, Catalysis}, number = {19}, publisher = {Wiley}, title = {{Cover Picture: The rigid core and flexible surface of amyloid fibrils probed by Magic‐Angle‐Spinning NMR spectroscopy of aromatic residues}}, doi = {10.1002/anie.202304138}, volume = {62}, year = {2023}, } @article{14036, abstract = {Magic-angle spinning (MAS) nuclear magnetic resonance (NMR) is establishing itself as a powerful method for the characterization of protein dynamics at the atomic scale. We discuss here how R1ρ MAS relaxation dispersion NMR can explore microsecond-to-millisecond motions. Progress in instrumentation, isotope labeling, and pulse sequence design has paved the way for quantitative analyses of even rare structural fluctuations. In addition to isotropic chemical-shift fluctuations exploited in solution-state NMR relaxation dispersion experiments, MAS NMR has a wider arsenal of observables, allowing to see motions even if the exchanging states do not differ in their chemical shifts. We demonstrate the potential of the technique for probing motions in challenging large enzymes, membrane proteins, and protein assemblies.}, author = {Napoli, Federico and Becker, Lea Marie and Schanda, Paul}, issn = {1879-033X}, journal = {Current Opinion in Structural Biology}, number = {10}, publisher = {Elsevier}, title = {{Protein dynamics detected by magic-angle spinning relaxation dispersion NMR}}, doi = {10.1016/j.sbi.2023.102660}, volume = {82}, year = {2023}, } @article{12114, abstract = {Probing the dynamics of aromatic side chains provides important insights into the behavior of a protein because flips of aromatic rings in a protein’s hydrophobic core report on breathing motion involving a large part of the protein. Inherently invisible to crystallography, aromatic motions have been primarily studied by solution NMR. The question how packing of proteins in crystals affects ring flips has, thus, remained largely unexplored. Here we apply magic-angle spinning NMR, advanced phenylalanine 1H-13C/2H isotope labeling and MD simulation to a protein in three different crystal packing environments to shed light onto possible impact of packing on ring flips. The flips of the two Phe residues in ubiquitin, both surface exposed, appear remarkably conserved in the different crystal forms, even though the intermolecular packing is quite different: Phe4 flips on a ca. 10–20 ns time scale, and Phe45 are broadened in all crystals, presumably due to µs motion. Our findings suggest that intramolecular influences are more important for ring flips than intermolecular (packing) effects.}, author = {Gauto, Diego F. and Lebedenko, Olga O. and Becker, Lea Marie and Ayala, Isabel and Lichtenecker, Roman and Skrynnikov, Nikolai R. and Schanda, Paul}, issn = {2590-1524}, journal = {Journal of Structural Biology: X}, keywords = {Structural Biology}, publisher = {Elsevier}, title = {{Aromatic ring flips in differently packed ubiquitin protein crystals from MAS NMR and MD}}, doi = {10.1016/j.yjsbx.2022.100079}, volume = {7}, year = {2023}, } @misc{12497, abstract = {Aromatic side chains are important reporters of the plasticity of proteins, and often form important contacts in protein–protein interactions. We studied aromatic residues in the two structurally homologous cross-β amyloid fibrils HET-s, and HELLF by employing a specific isotope-labeling approach and magic-angle-spinning NMR. The dynamic behavior of the aromatic residues Phe and Tyr indicates that the hydrophobic amyloid core is rigid, without any sign of "breathing motions" over hundreds of milliseconds at least. Aromatic residues exposed at the fibril surface have a rigid ring axis but undergo ring flips on a variety of time scales from nanoseconds to microseconds. Our approach provides direct insight into hydrophobic-core motions, enabling a better evaluation of the conformational heterogeneity generated from an NMR structural ensemble of such amyloid cross-β architecture.}, author = {Becker, Lea Marie and Schanda, Paul}, keywords = {aromatic side chains, isotopic labeling, protein dynamics, ring flips, spin relaxation}, publisher = {Institute of Science and Technology Austria}, title = {{Research data to: The rigid core and flexible surface of amyloid fibrils probed by magic-angle-spinning NMR spectroscopy of aromatic residues}}, doi = {10.15479/AT:ISTA:12497}, year = {2023}, } @article{12675, abstract = {Aromatic side chains are important reporters of the plasticity of proteins, and often form important contacts in protein--protein interactions. By studying a pair of structurally homologous cross-β amyloid fibrils, HET-s and HELLF, with a specific isotope-labeling approach and magic-angle-spinning (MAS) NMR, we have characterized the dynamic behavior of Phe and Tyr aromatic rings to show that the hydrophobic amyloid core is rigid, without any sign of "breathing motions" over hundreds of milliseconds at least. Aromatic residues exposed at the fibril surface have a rigid ring axis but undergo ring flips, on a variety of time scales from ns to µs. Our approach provides direct insight into hydrophobic-core motions, enabling a better evaluation of the conformational heterogeneity generated from a NMR structural ensemble of such amyloid cross-β architecture.}, author = {Becker, Lea Marie and Berbon, Mélanie and Vallet, Alicia and Grelard, Axelle and Morvan, Estelle and Bardiaux, Benjamin and Lichtenecker, Roman and Ernst, Matthias and Loquet, Antoine and Schanda, Paul}, issn = {1521-3773}, journal = {Angewandte Chemie International Edition}, keywords = {General Chemistry, Catalysis}, number = {19}, publisher = {Wiley}, title = {{The rigid core and flexible surface of amyloid fibrils probed by Magic‐Angle Spinning NMR of aromatic residues}}, doi = {10.1002/anie.202219314}, volume = {62}, year = {2023}, }