6rhy Citations

Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage.

Abstract

Formation of amyloid-beta (Aβ) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimer's disease (AD). Here, we present the three-dimensional structure of an Aβ oligomer formed in a membrane mimicking environment, namely an Aβ(1-42) tetramer, which comprises a six stranded β-sheet core. The two faces of the β-sheet core are hydrophobic and surrounded by the membrane-mimicking environment while the edges are hydrophilic and solvent-exposed. By increasing the concentration of Aβ(1-42) in the sample, Aβ(1-42) octamers are also formed, made by two Aβ(1-42) tetramers facing each other forming a β-sandwich structure. Notably, Aβ(1-42) tetramers and octamers inserted into lipid bilayers as well-defined pores. To establish oligomer structure-membrane activity relationships, molecular dynamics simulations were carried out. These studies revealed a mechanism of membrane disruption in which water permeation occurred through lipid-stabilized pores mediated by the hydrophilic residues located on the core β-sheets edges of the oligomers.

Reviews - 6rhy mentioned but not cited (2)

  1. Natural Compounds as Inhibitors of Aβ Peptide Aggregation: Chemical Requirements and Molecular Mechanisms. Pagano K, Tomaselli S, Molinari H, Ragona L. Front Neurosci 14 619667 (2020)
  2. Structural Studies Providing Insights into Production and Conformational Behavior of Amyloid-β Peptide Associated with Alzheimer's Disease Development. Urban AS, Pavlov KV, Kamynina AV, Okhrimenko IS, Arseniev AS, Bocharov EV. Molecules 26 2897 (2021)

Articles - 6rhy mentioned but not cited (14)



Reviews citing this publication (25)

  1. Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis. Nguyen PH, Ramamoorthy A, Sahoo BR, Zheng J, Faller P, Straub JE, Dominguez L, Shea JE, Dokholyan NV, De Simone A, Ma B, Nussinov R, Najafi S, Ngo ST, Loquet A, Chiricotto M, Ganguly P, McCarty J, Li MS, Hall C, Wang Y, Miller Y, Melchionna S, Habenstein B, Timr S, Chen J, Hnath B, Strodel B, Kayed R, Lesné S, Wei G, Sterpone F, Doig AJ, Derreumaux P. Chem Rev 121 2545-2647 (2021)
  2. Visualizing and trapping transient oligomers in amyloid assembly pathways. Cawood EE, Karamanos TK, Wilson AJ, Radford SE. Biophys Chem 268 106505 (2021)
  3. Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer's disease. Rudajev V, Novotny J. Front Mol Neurosci 15 937056 (2022)
  4. Exploring amyloid oligomers with peptide model systems. Samdin TD, Kreutzer AG, Nowick JS. Curr Opin Chem Biol 64 106-115 (2021)
  5. Interactions of Amyloid-β with Membrane Proteins. Wiatrak B, Piasny J, Kuźniarski A, Gąsiorowski K. Int J Mol Sci 22 6075 (2021)
  6. On the Role of Platelet-Generated Amyloid Beta Peptides in Certain Amyloidosis Health Complications. Inyushin M, Zayas-Santiago A, Rojas L, Kucheryavykh L. Front Immunol 11 571083 (2020)
  7. Studying protein structure and function by native separation-mass spectrometry. van Schaick G, Haselberg R, Somsen GW, Wuhrer M, Domínguez-Vega E. Nat Rev Chem 6 215-231 (2022)
  8. All roads lead to Rome - a review of the potential mechanisms by which exerkines exhibit neuroprotective effects in Alzheimer's disease. Liang YY, Zhang LD, Luo X, Wu LL, Chen ZW, Wei GH, Zhang KQ, Du ZA, Li RZ, So KF, Li A. Neural Regen Res 17 1210-1227 (2022)
  9. Amyloid Prefibrillar Oligomers: The Surprising Commonalities in Their Structure and Activity. Diociaiuti M, Bonanni R, Cariati I, Frank C, D'Arcangelo G. Int J Mol Sci 22 6435 (2021)
  10. Understanding and controlling amyloid aggregation with chirality. Foley AR, Raskatov JA. Curr Opin Chem Biol 64 1-9 (2021)
  11. Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease. Viles JH. Angew Chem Int Ed Engl 62 e202215785 (2023)
  12. An Overview of Several Inhibitors for Alzheimer's Disease: Characterization and Failure. Boopathi S, Poma AB, Garduño-Juárez R. Int J Mol Sci 22 10798 (2021)
  13. Single Molecule Characterization of Amyloid Oligomers. Yang J, Perrett S, Wu S. Molecules 26 948 (2021)
  14. Cell-Penetrating Peptides with Unexpected Anti-Amyloid Properties. Österlund N, Wärmländer SKTS, Gräslund A. Pharmaceutics 14 823 (2022)
  15. Effect of the Lipid Landscape on the Efficacy of Cell-Penetrating Peptides. Zakany F, Mándity IM, Varga Z, Panyi G, Nagy P, Kovacs T. Cells 12 1700 (2023)
  16. Flanking regions, amyloid cores, and polymorphism: the potential interplay underlying structural diversity. Bhopatkar AA, Kayed R. J Biol Chem 299 105122 (2023)
  17. Oligomer Formation by Amyloid-β42 in a Membrane-Mimicking Environment in Alzheimer's Disease. Rosenberry TL, Zhou HX, Stagg SM, Paravastu AK. Molecules 27 8804 (2022)
  18. Structural polymorphism and cytotoxicity of brain-derived β-amyloid extracts. Al Adem K, Lee S. Protein Sci 32 e4639 (2023)
  19. Conformational Essentials Responsible for Neurotoxicity of Aβ42 Aggregates Revealed by Antibodies against Oligomeric Aβ42. Song C, Zhang T, Zhang Y. Molecules 27 6751 (2022)
  20. Fatal Attraction: The Case of Toxic Soluble Dimers of Truncated PQBP-1 Mutants in X-Linked Intellectual Disability. Chen YW, Rahman SK. Int J Mol Sci 22 2240 (2021)
  21. Viroporins vs. Other Pore-Forming Proteins: What Lessons Can We Take? Žerovnik E. Front Chem 9 626059 (2021)
  22. Aβ-Targeting Bifunctional Chelators (BFCs) for Potential Therapeutic and PET Imaging Applications. Krasnovskaya O, Kononova A, Erofeev A, Gorelkin P, Majouga A, Beloglazkina E. Int J Mol Sci 24 236 (2022)
  23. Imaging Amyloid-β Membrane Interactions: Ion-Channel Pores and Lipid-Bilayer Permeability in Alzheimer's Disease. Viles JH. Angew Chem Weinheim Bergstr Ger 135 e202215785 (2023)
  24. Purinergic signaling via P2X receptors and mechanisms of unregulated ATP release in the outer retina and age-related macular degeneration. Molcak H, Jiang K, Campbell CJ, Matsubara JA. Front Neurosci 17 1216489 (2023)
  25. Recent Computational Advances Regarding Amyloid-β and Tau Membrane Interactions in Alzheimer's Disease. Nguyen PH, Derreumaux P. Molecules 28 7080 (2023)

Articles citing this publication (49)



Related citations provided by authors (1)