Does Aluminium Bind to Histidine? An NMR Investigation of Amyloid β12 and Amyloid β16 Fragments

Priya Narayan, Bankala Krishnarjuna, Vinaya Vishwanathan, Dasappa Jagadeesh Kumar, Sudhir Babu, Krishna Venkatachala Ramanathan, Kalpathy Ramaier Katchap Easwaran, Holenarasipur Gundurao Nagendra, Srinivasarao Raghothama

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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.

Original languageEnglish
Pages (from-to)48-59
Number of pages12
JournalChemical Biology & Drug Design
Volume82
Issue number1
DOIs
Publication statusPublished - 1 Jul 2013
Externally publishedYes

Keywords

  • Aβ peptides
  • Aluminium interactions
  • Alzheimer's disease
  • Amyloid peptides
  • Metal binding
  • NMR

Cite this

Narayan, P., Krishnarjuna, B., Vishwanathan, V., Jagadeesh Kumar, D., Babu, S., Ramanathan, K. V., Easwaran, K. R. K., Nagendra, H. G., & Raghothama, S. (2013). Does Aluminium Bind to Histidine? An NMR Investigation of Amyloid β12 and Amyloid β16 Fragments. Chemical Biology & Drug Design, 82(1), 48-59. https://doi.org/10.1111/cbdd.12129