PMID- 10413512 OWN - NLM STAT- MEDLINE DCOM- 19990915 LR - 20131121 IS - 0006-2960 (Print) IS - 0006-2960 (Linking) VI - 38 IP - 29 DP - 1999 Jul 20 TI - Histidine-13 is a crucial residue in the zinc ion-induced aggregation of the A beta peptide of Alzheimer's disease. PG - 9373-8 AB - Metal ions such as Zn(2+) and Cu(2+) have been implicated in both the aggregation and neurotoxicity of the beta-amyloid (Abeta) peptide that is present in the brains of Alzheimer's sufferers. Zinc ions in particular have been shown to induce rapid aggregation of Abeta. Rat Abeta binds zinc ions much less avidly than human Abeta, and rats do not form cerebral Abeta amyloid. Rat Abeta differs from human Abeta by the substitution of Gly for Arg, Phe for Tyr, and Arg for His at positions 5, 10, and 13, respectively. Through the use of synthetic peptides corresponding to the first 28 residues of human Abeta, rat Abeta, and single-residue variations, we use circular dichroism spectroscopy, sedimentation assays, and immobilized metal ion affinity chromatography to show that the substitution of Arg for His-13 is responsible for the different Zn(2+)-induced aggregation behavior of rat and human Abeta. The coordination of Zn(2+) to histidine-13 is critical to the zinc ion induced aggregation of Abeta. FAU - Liu, S T AU - Liu ST AD - School of Chemistry, Department of Biochemistry and Molecular Biology, The University of Melbourne, Parkville, Victoria, Australia. FAU - Howlett, G AU - Howlett G FAU - Barrow, C J AU - Barrow CJ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochemistry JT - Biochemistry JID - 0370623 RN - 0 (Amyloid beta-Peptides) RN - 0 (Cations, Divalent) RN - 0 (Chelating Agents) RN - 0 (Peptide Fragments) RN - 0 (Solutions) RN - 0 (amyloid beta-protein (1-28)) RN - 4QD397987E (Histidine) RN - J41CSQ7QDS (Zinc) SB - IM MH - Alzheimer Disease/*metabolism MH - Amino Acid Sequence MH - Amino Acid Substitution MH - Amyloid beta-Peptides/chemistry/*metabolism MH - Animals MH - Cations, Divalent/chemistry/metabolism MH - Chelating Agents/chemistry/metabolism MH - Chromatography, High Pressure Liquid MH - Circular Dichroism MH - Dose-Response Relationship, Drug MH - Histidine/chemistry/*metabolism MH - Humans MH - Molecular Sequence Data MH - Peptide Fragments/chemistry/metabolism MH - Protein Structure, Secondary MH - Rats MH - Solutions MH - Zinc/chemistry/*metabolism EDAT- 1999/07/22 00:00 MHDA- 1999/07/22 00:01 CRDT- 1999/07/22 00:00 PHST- 1999/07/22 00:00 [pubmed] PHST- 1999/07/22 00:01 [medline] PHST- 1999/07/22 00:00 [entrez] AID - 10.1021/bi990205o [doi] AID - bi990205o [pii] PST - ppublish SO - Biochemistry. 1999 Jul 20;38(29):9373-8. doi: 10.1021/bi990205o.