Three Long-Range Distance Constraints and an Approach Towards a Model for the α-Synuclein-Fibril Fold

Verfasser / Beitragende:
[Maryam Hashemi Shabestari, Pravin Kumar, Ine Segers-Nolten, Mireille Claessens, Bart van Rooijen, Vinod Subramaniam, Martina Huber]
Ort, Verlag, Jahr:
2015
Enthalten in:
Applied Magnetic Resonance, 46/4(2015-04-01), 369-388
Format:
Artikel (online)
ID: 605545944
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024 7 0 |a 10.1007/s00723-014-0622-7  |2 doi 
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245 0 0 |a Three Long-Range Distance Constraints and an Approach Towards a Model for the α-Synuclein-Fibril Fold  |h [Elektronische Daten]  |c [Maryam Hashemi Shabestari, Pravin Kumar, Ine Segers-Nolten, Mireille Claessens, Bart van Rooijen, Vinod Subramaniam, Martina Huber] 
520 3 |a 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. 
540 |a Springer-Verlag Wien, 2015 
700 1 |a Hashemi Shabestari  |D Maryam  |u Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands  |4 aut 
700 1 |a Kumar  |D Pravin  |u Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands  |4 aut 
700 1 |a Segers-Nolten  |D Ine  |u Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands  |4 aut 
700 1 |a Claessens  |D Mireille  |u Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands  |4 aut 
700 1 |a van Rooijen  |D Bart  |u Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands  |4 aut 
700 1 |a Subramaniam  |D Vinod  |u Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands  |4 aut 
700 1 |a Huber  |D Martina  |u Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands  |4 aut 
773 0 |t Applied Magnetic Resonance  |d Springer Vienna  |g 46/4(2015-04-01), 369-388  |x 0937-9347  |q 46:4<369  |1 2015  |2 46  |o 723 
856 4 0 |u https://doi.org/10.1007/s00723-014-0622-7  |q text/html  |z Onlinezugriff via DOI 
898 |a BK010053  |b XK010053  |c XK010000 
900 7 |a Metadata rights reserved  |b Springer special CC-BY-NC licence  |2 nationallicence 
908 |D 1  |a research-article  |2 jats 
949 |B NATIONALLICENCE  |F NATIONALLICENCE  |b NL-springer 
950 |B NATIONALLICENCE  |P 856  |E 40  |u https://doi.org/10.1007/s00723-014-0622-7  |q text/html  |z Onlinezugriff via DOI 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Hashemi Shabestari  |D Maryam  |u Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Kumar  |D Pravin  |u Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Segers-Nolten  |D Ine  |u Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Claessens  |D Mireille  |u Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a van Rooijen  |D Bart  |u Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Subramaniam  |D Vinod  |u Nanobiophysics, MESA+Institute for Nanotechnology, University of Twente, PO Box 217, 7500 AE, Enschede, The Netherlands  |4 aut 
950 |B NATIONALLICENCE  |P 700  |E 1-  |a Huber  |D Martina  |u Huygens-Kammerlingh-Onnes Laboratory, Department of Physics, Leiden University, PO Box 9504, 2300 RA, Leiden, The Netherlands  |4 aut 
950 |B NATIONALLICENCE  |P 773  |E 0-  |t Applied Magnetic Resonance  |d Springer Vienna  |g 46/4(2015-04-01), 369-388  |x 0937-9347  |q 46:4<369  |1 2015  |2 46  |o 723