title: Does aluminium bind to histidine? An NMR investigation of amyloid β12 and amyloid β16 fragments.
abstract: Aluminium and zinc are known to be the major triggering agents for aggregation of amyloid peptides leading to plaque formation in Alzheimer's disease. While zinc binding to histidine in Aβ (amyloid β) fragments has been implicated as responsible for aggregation, not much information is available on the interaction of aluminium with histidine. In the NMR study of the N-terminal Aβ fragments, DAEFRHDSGYEV (Aβ12) and DAEFRHDSGYEVHHQK (Aβ16) presented here, the interactions of the fragments with aluminium have been investigated. Significant chemical shifts were observed for few residues near the C-terminus when aluminium chloride was titrated with Aβ12 and Aβ16 peptides. Surprisingly, it is nonhistidine residues which seem to be involved in aluminium binding. Based on NMR constrained structure obtained by molecular modelling, aluminium-binding pockets in Aβ12 were around charged residues such as Asp, Glu. The results are discussed in terms of native structure propagation, and the relevance of histidine residues in the sequences for metal-binding interactions. We expect that the study of such short amyloid peptide fragments will not only provide clues for plaque formation in aggregated conditions but also facilitate design of potential drugs for these targets.
authors: Department of Biotechnology, Sir M. Visvesvaraya Institute of Technology, Bangalore, 562157, India.
authors: Priya
authors: P
authors: Narayan
authors: Bankala
authors: B
authors: Krishnarjuna
authors: Vinaya
authors: V
authors: Vishwanathan
authors: Dasappa
authors: D
authors: Jagadeesh Kumar
authors: Sudhir
authors: S
authors: Babu
authors: Krishna Venkatachala
authors: KV
authors: Ramanathan
authors: Kalpathy Ramaier Katchap
authors: KR
authors: Easwaran
authors: Holenarasipur Gundurao
authors: HG
authors: Nagendra
authors: Srinivasarao
authors: S
authors: Raghothama
mesh_terms: D000535:Aluminum / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D006639:Histidine / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C542321:amyloid beta-protein (1-12); C433241:amyloid beta-protein (1-16); D006639:Histidine; D000535:Aluminum