A long‐lived Aβ oligomer resistant to fibrillization

Nick, Mimi; Wu, Yibing; Schmidt, Nathan W.; Prusiner, Stanley B.; Stöhr, Jan; DeGrado, William F.

doi:10.1002/bip.23096

A long‐lived Aβ oligomer resistant to fibrillization

Journal Article · Tue Jan 09 19:00:00 EST 2018 · Biopolymers

DOI:https://doi.org/10.1002/bip.23096· OSTI ID:1416592

Nick, Mimi ^[1]; Wu, Yibing ^[1]; Schmidt, Nathan W. ^[1]; Prusiner, Stanley B. ^[2]; Stöhr, Jan ^[3]; ^[1]

Department of Pharmaceutical Chemistry University of California San Francisco California
Institute for Neurodegenerative Diseases and Department of Neurology Weill Institute for Neurosciences, University of California San Francisco California, Department of Biochemistry and Biophysics University of California San Francisco California
Institute for Neurodegenerative Diseases and Department of Neurology Weill Institute for Neurosciences, University of California San Francisco California

Abstract

The hydrophobic Aβ peptide is highly aggregation prone; it first forms soluble oligomers, which then convert into the amyloid fibrils found in the cerebral plaques of Alzheimer's disease. It is generally understood that as the peptide concentration of Aβ increases, the fibrillization process is accelerated, but we examine the limits on this phenomenon. We found that once a threshold concentration of Aβ is exceeded, a stable oligomer is formed at the expense of fibril formation. The suppression of fibril formation was observed by amyloid‐binding dye Thioflavin T and solution nuclear magnetic resonance (NMR). Small‐angle X‐ray scattering, size exclusion chromatography, and analytical ultracentrifugation demonstrated that Aβ peptides form a range of compact species, with a dimer being an early highly populated oligomer. Solution NMR allowed us to define the secondary structure of this Aβ dimer, which shows interlocking contacts between C‐terminal peptide strands. Thus, we present a novel Aβ oligomer that resists conversion to fibrils and remains stable for more than one year.

View Accepted Manuscript (Publisher)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-76SF00515

OSTI ID:: 1416592

Journal Information:: Biopolymers, Journal Name: Biopolymers Journal Issue: 8 Vol. 109; ISSN 0006-3525

Publisher:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: United States

Language:: English

References (35)

1-Anilino-8-naphthalene sulfonate as a protein conformational tightening agent Matulis, Daumantas; Baumann, Christoph G.; Bloomfield, Victor A. Biopolymers, Vol. 49, Issue 6 https://doi.org/10.1002/(SICI)1097-0282(199905)49:6<451::AID-BIP3>3.0.CO;2-6	journal	May 1999
An Asymmetric Dimer as the Basic Subunit in Alzheimer’s Disease Amyloid β Fibrils Lopez del Amo, Juan Miguel; Schmidt, Matthias; Fink, Uwe Angewandte Chemie International Edition, Vol. 51, Issue 25 https://doi.org/10.1002/anie.201200965	journal	May 2012
Atomic-Resolution Three-Dimensional Structure of Amyloid β Fibrils Bearing the Osaka Mutation Schütz, Anne K.; Vagt, Toni; Huber, Matthias Angewandte Chemie International Edition, Vol. 54, Issue 1 https://doi.org/10.1002/anie.201408598	journal	November 2014
Size-Distribution Analysis of Macromolecules by Sedimentation Velocity Ultracentrifugation and Lamm Equation Modeling Schuck, Peter Biophysical Journal, Vol. 78, Issue 3 https://doi.org/10.1016/S0006-3495(00)76713-0	journal	March 2000
Calculating Sedimentation Coefficient Distributions by Direct Modeling of Sedimentation Velocity Concentration Profiles Dam, Julie; Schuck, Peter Methods in Enzymology https://doi.org/10.1016/S0076-6879(04)84012-6	book	January 2004
Sedimentation Velocity Analysis of Amyloid Oligomers and Fibrils Mok, Yee‐Foong; Howlett, Geoffrey J. Amyloid, Prions, and Other Protein Aggregates, Part C https://doi.org/10.1016/S0076-6879(06)13011-6	book	January 2006
Off-pathway aggregation can inhibit fibrillation at high protein concentrations Deva, Taru; Lorenzen, Nikolai; Vad, Brian S. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, Vol. 1834, Issue 3 https://doi.org/10.1016/j.bbapap.2012.12.020	journal	March 2013
Fibrillar seeds alleviate amyloid-β cytotoxicity by omitting formation of higher-molecular-weight oligomers Wu, Wei-hui; Liu, Qian; Sun, Xun Biochemical and Biophysical Research Communications, Vol. 439, Issue 3 https://doi.org/10.1016/j.bbrc.2013.08.088	journal	September 2013
Structural differences between amyloid beta oligomers Breydo, Leonid; Kurouski, Dmitry; Rasool, Suhail Biochemical and Biophysical Research Communications, Vol. 477, Issue 4 https://doi.org/10.1016/j.bbrc.2016.06.122	journal	September 2016
Molecular Structure of β-Amyloid Fibrils in Alzheimer’s Disease Brain Tissue Lu, Jun-Xia; Qiang, Wei; Yau, Wai-Ming Cell, Vol. 154, Issue 6 https://doi.org/10.1016/j.cell.2013.08.035	journal	September 2013
Biophysical characterization data on Aβ soluble oligomers produced through a method enabling prolonged oligomer stability and biological buffer conditions Crisostomo, Amanda C.; Dang, Loan; Digambaranath, Jyothi L. Data in Brief, Vol. 4 https://doi.org/10.1016/j.dib.2015.07.034	journal	September 2015
Aβ-globulomers are formed independently of the fibril pathway Gellermann, Gerald P.; Byrnes, Helga; Striebinger, Andreas Neurobiology of Disease, Vol. 30, Issue 2 https://doi.org/10.1016/j.nbd.2008.01.010	journal	May 2008
Structural Transformations of Oligomeric Intermediates in the Fibrillation of the Immunoglobulin Light Chain LEN ^† Souillac, Pierre O.; Uversky, Vladimir N.; Fink, Anthony L. Biochemistry, Vol. 42, Issue 26 https://doi.org/10.1021/bi034652m	journal	July 2003
Capturing Intermediate Structures of Alzheimer's β-Amyloid, Aβ(1−40), by Solid-State NMR Spectroscopy Chimon, Sandra; Ishii, Yoshitaka Journal of the American Chemical Society, Vol. 127, Issue 39 https://doi.org/10.1021/ja054039l	journal	October 2005
Structural Insight into an Alzheimer’s Brain-Derived Spherical Assembly of Amyloid β by Solid-State NMR Parthasarathy, Sudhakar; Inoue, Masafumi; Xiao, Yiling Journal of the American Chemical Society, Vol. 137, Issue 20 https://doi.org/10.1021/jacs.5b03373	journal	May 2015
Structural Polymorphism of Alzheimer’s β-Amyloid Fibrils as Controlled by an E22 Switch: A Solid-State NMR Study Elkins, Matthew R.; Wang, Tuo; Nick, Mimi Journal of the American Chemical Society, Vol. 138, Issue 31 https://doi.org/10.1021/jacs.6b03715	journal	July 2016
A pH-Induced Switch in Human Glucagon-like Peptide-1 Aggregation Kinetics Zapadka, Karolina L.; Becher, Frederik J.; Uddin, Shahid Journal of the American Chemical Society, Vol. 138, Issue 50 https://doi.org/10.1021/jacs.6b05025	journal	December 2016
A specific amyloid-β protein assembly in the brain impairs memory Lesné, Sylvain; Koh, Ming Teng; Kotilinek, Linda Nature, Vol. 440, Issue 7082 https://doi.org/10.1038/nature04533	journal	March 2006
Atomic-resolution dynamics on the surface of amyloid-β protofibrils probed by solution NMR Fawzi, Nicolas L.; Ying, Jinfa; Ghirlando, Rodolfo Nature, Vol. 480, Issue 7376 https://doi.org/10.1038/nature10577	journal	October 2011
Structural variation in amyloid-β fibrils from Alzheimer's disease clinical subtypes Qiang, Wei; Yau, Wai-Ming; Lu, Jun-Xia Nature, Vol. 541, Issue 7636 https://doi.org/10.1038/nature20814	journal	January 2017
Molecular mechanisms of protein aggregation from global fitting of kinetic models Meisl, Georg; Kirkegaard, Julius B.; Arosio, Paolo Nature Protocols, Vol. 11, Issue 2 https://doi.org/10.1038/nprot.2016.010	journal	January 2016
Structural conversion of neurotoxic amyloid-β1–42 oligomers to fibrils Ahmed, Mahiuddin; Davis, Judianne; Aucoin, Darryl Nature Structural & Molecular Biology, Vol. 17, Issue 5 https://doi.org/10.1038/nsmb.1799	journal	April 2010
Aβ(1–42) fibril structure illuminates self-recognition and replication of amyloid in Alzheimer's disease Xiao, Yiling; Ma, Buyong; McElheny, Dan Nature Structural & Molecular Biology, Vol. 22, Issue 6 https://doi.org/10.1038/nsmb.2991	journal	May 2015
High-resolution NMR characterization of low abundance oligomers of amyloid-β without purification Kotler, Samuel A.; Brender, Jeffrey R.; Vivekanandan, Subramanian Scientific Reports, Vol. 5, Issue 1 https://doi.org/10.1038/srep11811	journal	July 2015
3D structure of Alzheimer's amyloid- (1-42) fibrils Luhrs, T.; Ritter, C.; Adrian, M. Proceedings of the National Academy of Sciences, Vol. 102, Issue 48 https://doi.org/10.1073/pnas.0506723102	journal	November 2005
Molecular structural basis for polymorphism in Alzheimer's -amyloid fibrils Paravastu, A. K.; Leapman, R. D.; Yau, W. -M. Proceedings of the National Academy of Sciences, Vol. 105, Issue 47 https://doi.org/10.1073/pnas.0806270105	journal	November 2008
Antiparallel -sheet architecture in Iowa-mutant -amyloid fibrils Qiang, W.; Yau, W. -M.; Luo, Y. Proceedings of the National Academy of Sciences, Vol. 109, Issue 12 https://doi.org/10.1073/pnas.1111305109	journal	March 2012
Toxic fibrillar oligomers of amyloid- have cross- structure Stroud, J. C.; Liu, C.; Teng, P. K. Proceedings of the National Academy of Sciences, Vol. 109, Issue 20 https://doi.org/10.1073/pnas.1203193109	journal	April 2012
Accelerating Amyloid-β Fibrillization Reduces Oligomer Levels and Functional Deficits in Alzheimer Disease Mouse Models Cheng, Irene H.; Scearce-Levie, Kimberly; Legleiter, Justin Journal of Biological Chemistry, Vol. 282, Issue 33 https://doi.org/10.1074/jbc.M701078200	journal	June 2007
The aggregation kinetics of Alzheimer's β-amyloid peptide is controlled by stochastic nucleation Hortschansky, Peter; Schroeckh, Volker; Christopeit, Tony Protein Science, Vol. 14, Issue 7 https://doi.org/10.1110/ps.041266605	journal	July 2005
Common Structure of Soluble Amyloid Oligomers Implies Common Mechanism of Pathogenesis Kayed, R. Science, Vol. 300, Issue 5618 https://doi.org/10.1126/science.1079469	journal	April 2003
Self-Propagating, Molecular-Level Polymorphism in Alzheimer's -Amyloid Fibrils Petkova, A. T. Science, Vol. 307, Issue 5707 https://doi.org/10.1126/science.1105850	journal	January 2005
Amyloid-β peptide protects against microbial infection in mouse and worm models of Alzheimer’s disease Kumar, Deepak Kumar Vijaya; Choi, Se Hoon; Washicosky, Kevin J. Science Translational Medicine, Vol. 8, Issue 340 https://doi.org/10.1126/scitranslmed.aaf1059	journal	May 2016
Mechanisms of Protein Fibril Formation: Nucleated Polymerization with Competing Off-Pathway Aggregation Powers, Evan T.; Powers, David L. Biophysical Journal, Vol. 94, Issue 2 https://doi.org/10.1529/biophysj.107.117168	journal	January 2008
Alzheimer's disease: the potential therapeutic role of the natural antibiotic amyloid-β peptide Kumar, Deepak Kumar Vijaya; Eimer, William A.; Tanzi, Rudolph E. Neurodegenerative Disease Management, Vol. 6, Issue 5 https://doi.org/10.2217/nmt-2016-0035	journal	October 2016

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