A beta under stress: the effects of acidosis, Cu2+-binding, and oxidation on amyloid beta-peptide dimers

LIAO, Q.H., Michael Christopher OWEN, S. BALI, B. BARZ and B. STRODEL. A beta under stress: the effects of acidosis, Cu2+-binding, and oxidation on amyloid beta-peptide dimers. Chemical communications. Cambridge: Royal Society of Chemistry, 2018, vol. 54, No 56, p. 7766-7769. ISSN 1359-7345. Available from: https://dx.doi.org/10.1039/c8cc02263a.

Basic information

• Original name: A beta under stress: the effects of acidosis, Cu2+-binding, and oxidation on amyloid beta-peptide dimers
• Authors: LIAO, Q.H. (276 Germany), Michael Christopher OWEN (124 Canada, guarantor, belonging to the institution), S. BALI (276 Germany), B. BARZ (276 Germany) and B. STRODEL (276 Germany).
• Edition: Chemical communications, Cambridge, Royal Society of Chemistry, 2018, 1359-7345.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10608 Biochemistry and molecular biology
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 6.164
• RIV identification code: RIV/00216224:14740/18:00106574
• Organization unit: Central European Institute of Technology
• Doi: http://dx.doi.org/10.1039/c8cc02263a
• UT WoS: 000438237700008
• Keywords in English: ALZHEIMERS-DISEASE; PROTEIN OLIGOMERS; FIBRIL FORMATION; AGGREGATION; TOXICITY; PATHWAYS; ASSEMBLIES; DYNAMICS; MONOMER; BINDING
• Tags: rivok
• Tags: International impact, Reviewed

Abstract

In light of the high affinity of Cu2+ for Alzheimer's A(1-42) and its ability to subsequently catalyze the formation of radicals, we examine the effects of Cu2+ binding, A oxidation, and an acidic environment on the conformational dynamics of the smallest A(1-42) oligomer, the A(1-42) dimer. Transition networks calculated from Hamiltonian replica exchange molecular dynamics (H-REMD) simulations reveal that the decreased pH considerably increased the -sheet content, whereas Cu2+ binding increased the exposed hydrophobic surface area, both of which can contribute to an increased oligomerization propensity and toxicity.