caa a22 4500 605545944 CHVBK 20210128100938.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s00723-014-0622-7 doi (NATIONALLICENCE)springer-10.1007/s00723-014-0622-7 Three Long-Range Distance Constraints and an Approach Towards a Model for the α-Synuclein-Fibril Fold [Elektronische Daten] [Maryam Hashemi Shabestari, Pravin Kumar, Ine Segers-Nolten, Mireille Claessens, Bart van Rooijen, Vinod Subramaniam, Martina Huber] Amyloid fibrils and plaques are the hallmark of neurodegenerative diseases. In Parkinson's disease, plaques (Lewy bodies) consist predominantly of the α-synuclein (αS) protein. To understand aggregation, the molecular architecture of αS fibrils needs to be known. Here, we determine nm-distance constraints for the protein in the fibril by double electron-electron paramagnetic resonance (DEER) on doubly spin-labeled αS variants, diamagnetically diluted with wild-type αS to suppress intermolecular interactions. Intramolecular distances in three pairs (56/69, 56/90 and 69/90) are reported. An approach to derive a model for the fibril fold from sparse distance data assuming only parallel β-sheets is described. Using the distances obtained in this study as input, a model is obtained with three strands, comprising residues 56-90, in which the strands consist of 8-12 residues each. Limitations of the approach are discussed in detail, showing that the interpretation of the data does not yet yield an unambiguous structure model. Possible avenues to improve this situation are described. Springer-Verlag Wien, 2015 Hashemi Shabestari Maryam Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands aut Kumar Pravin Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands aut Segers-Nolten Ine Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands aut Claessens Mireille Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands aut van Rooijen Bart Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands aut Subramaniam Vinod Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands aut Huber Martina Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands aut Applied Magnetic Resonance Springer Vienna 46/4(2015-04-01), 369-388 0937-9347 46:4<369 2015 46 723 https://doi.org/10.1007/s00723-014-0622-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00723-014-0622-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Hashemi Shabestari Maryam Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Kumar Pravin Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands aut NATIONALLICENCE 700 1- Segers-Nolten Ine Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands aut NATIONALLICENCE 700 1- Claessens Mireille Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands aut NATIONALLICENCE 700 1- van Rooijen Bart Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands aut NATIONALLICENCE 700 1- Subramaniam Vinod Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands aut NATIONALLICENCE 700 1- Huber Martina Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands aut NATIONALLICENCE 773 0- Applied Magnetic Resonance Springer Vienna 46/4(2015-04-01), 369-388 0937-9347 46:4<369 2015 46 723