Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease
Yiling Xiao,Buyong Ma,Dan McElheny,Sudhakar Parthasarathy,Fei Long,Minako Hoshi,Ruth Nussinov,Yoshitaka Ishii +7 more
TLDR
The atomic model of an Aβ(1–42) amyloid fibril, from solid-state NMR (ssNMR) data, is presented, providing insight into the A β(1-42)-selective self-replicating amyloids-propagation machinery in early-stage Alzheimer's disease.Abstract:
Aβ(1–42) is the most pathogenic amyloid-β species in Alzheimer's disease (AD). The solid-state NMR–based atomic model of an Aβ(1–42) fibril elucidates the mechanism of fibril formation and propagation in AD and other amyloid diseases.read more
Citations
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Journal ArticleDOI
Solid-state NMR structure of a pathogenic fibril of full-length human α-synuclein
Marcus D. Tuttle,Marcus D. Tuttle,Gemma Comellas,Andrew J. Nieuwkoop,Andrew J. Nieuwkoop,Dustin J. Covell,Deborah A. Berthold,Kathryn D. Kloepper,Kathryn D. Kloepper,Joseph M. Courtney,Jae K Kim,Alexander M. Barclay,Amy Kendall,William Wan,William Wan,Gerald Stubbs,Charles D. Schwieters,Virginia M.-Y. Lee,Jimin George,Chad M. Rienstra +19 more
TL;DR: A high-resolution structure of an α-synuclein fibril, in a form that induces robust pathology in primary neuronal culture, determined by solid-state NMR spectroscopy and validated by EM and X-ray fiber diffraction is presented.
Journal ArticleDOI
Fibril structure of amyloid-β(1-42) by cryo-electron microscopy.
Lothar Gremer,Lothar Gremer,Daniel Schölzel,Daniel Schölzel,Carla Schenk,Elke Reinartz,Jörg Labahn,Jörg Labahn,Raimond B. G. Ravelli,Markus Tusche,Carmen López-Iglesias,Wolfgang Hoyer,Wolfgang Hoyer,Henrike Heise,Henrike Heise,Dieter Willbold,Dieter Willbold,Gunnar F. Schröder,Gunnar F. Schröder +18 more
TL;DR: The complete structure of an Aβ(1–42) fibril composed of two intertwined protofilaments determined by cryo–electron microscopy (cryo-EM) and provides a structural basis for understanding the effect of several disease-causing and disease-preventing mutations.
Journal ArticleDOI
Atomic-resolution structure of a disease-relevant Aβ(1–42) amyloid fibril
Marielle A. Wälti,Francesco Ravotti,Hiromi Arai,Charles G. Glabe,Joseph S. Wall,Anja Böckmann,Peter Güntert,Beat H. Meier,Roland Riek +8 more
TL;DR: The 3D structure of a disease-relevant Aβ(1–42) fibril polymorph is determined combining data from solid-state NMR spectroscopy and mass-per-length measurements from EM, forming a double-horseshoe–like cross–β-sheet entity with maximally buried hydrophobic side chains.
Journal ArticleDOI
Atomic Resolution Structure of Monomorphic Aβ42 Amyloid Fibrils
Michael T. Colvin,Robert Silvers,Qing Zhe Ni,Thach V. Can,Ivan V. Sergeyev,Melanie Rosay,Kevin J. Donovan,Brian Michael,Joseph S. Wall,Sara Linse,Robert G. Griffin +10 more
TL;DR: The structure provides a point of departure for the design of drugs that bind to the fibril surface and therefore interfere with secondary nucleation and for other therapeutic approaches to mitigate Aβ42 aggregation.
Journal ArticleDOI
A new era for understanding amyloid structures and disease.
TL;DR: The first near-atomic-resolution structures of amyloid fibrils formed in vitro, seeded from plaque material and analysed directly ex vivo are now available and reveal cross-β structures that are far more intricate than anticipated.
References
More filters
Journal ArticleDOI
NMRPipe: a multidimensional spectral processing system based on UNIX pipes
TL;DR: The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks.
Journal ArticleDOI
Alzheimer's Disease: Genes, Proteins, and Therapy
TL;DR: Evidence that the presenilin proteins, mutations in which cause the most aggressive form of inherited AD, lead to altered intramembranous cleavage of the beta-amyloid precursor protein by the protease called gamma-secretase has spurred progress toward novel therapeutics and provided discrete biochemical targets for drug screening and development.
Journal ArticleDOI
AQUA and PROCHECK-NMR: programs for checking the quality of protein structures solved by NMR
TL;DR: The AQUA and PROCHECK-NMR programs provide a means of validating the geometry and restraint violations of an ensemble of protein structures solved by solution NMR, and their outputs include a detailed breakdown of the restraint violations.
Journal ArticleDOI
Protein folding and misfolding
TL;DR: The manner in which a newly synthesized chain of amino acids transforms itself into a perfectly folded protein depends both on the intrinsic properties of the amino-acid sequence and on multiple contributing influences from the crowded cellular milieu.
Journal ArticleDOI
3D structure of Alzheimer's amyloid-β(1–42) fibrils
Thorsten Lührs,Christiane Ritter,Marc Adrian,Dominique Riek-Loher,Bernd Bohrmann,Heinz Döbeli,David Schubert,Roland Riek +7 more
TL;DR: The 3D structure of the fibrils comprising Aβ(1–42), which was obtained by using hydrogen-bonding constraints from quenched hydrogen/deuterium-exchange NMR, side-chain packing constraints from pairwise mutagenesis studies, and parallel, in-register β-sheet arrangement from previous solid-state NMR studies, explains the sequence selectivity, the cooperativity, and the apparent unidirectionality of Aβ fibril growth.