biostudies-literatureDong JNIA NIH HHSNINDS NIH HHSNIGMS NIH HHS13313-8https://www.ebi.ac.uk/biostudies/studies/S-EPMC1948904biostudies-literatureUnknown104(33)Protein and peptide assembly into amyloid has been implicated in functions that range from beneficial epigenetic controls to pathological etiologies. However, the exact structures of the assemblies that regulate biological activity remain poorly defined. We have previously used Zn(2+) to modulate the assembly kinetics and morphology of congeners of the amyloid beta peptide (Abeta) associated with Alzheimer's disease. We now reveal a correlation among Abeta-Cu(2+) coordination, peptide self-assembly, and neuronal viability. By using the central segment of Abeta, HHQKLVFFA or Abeta(13-21), which contains residues H13 and H14 implicated in Abeta-metal ion binding, we show that Cu(2+) forms complexes with Abeta(13-21) and its K16A mutant and that the complexes, which do not self-assemble into Proceedings of the National Academy of Sciences of the United States of AmericaEngineering metal ion coordination to regulate amyloid fibril assembly and toxicity.PMC1948904NS048254P50 AG025688R01 AG023695R01 NS048254GM42025R01 GM042025AG023695Lynn DGShokes JEWarncke KDong JChilders WSTian BMehta AKCanfield JMSimmons JAScott RAMao ZfalseEngineering metal ion coordination to regulate amyloid fibril assembly and toxicity.Protein and peptide assembly into amyloid has been implicated in functions that range from beneficial epigenetic controls to pathological etiologies. However, the exact structures of the assemblies that regulate biological activity remain poorly defined. We have previously used Zn(2+) to modulate the assembly kinetics and morphology of congeners of the amyloid beta peptide (Abeta) associated with Alzheimer's disease. We now reveal a correlation among Abeta-Cu(2+) coordination, peptide self-assembly, and neuronal viability. By using the central segment of Abeta, HHQKLVFFA or Abeta(13-21), which contains residues H13 and H14 implicated in Abeta-metal ion binding, we show that Cu(2+) forms complexes with Abeta(13-21) and its K16A mutant and that the complexes, which do not self-assemble into 2007-01-01T00:00:00Z2007 Aug2025-04-05T15:29:19.442Z2019-03-27T02:21:17ZS-EPMC19489041768698210.1073/pnas.0702669104