Molecular Insights into Human Serum Albumin as a Receptor of Amyloid-β in the Extracellular Region

Tae Su Choi, Hyuck Jin Lee, Jong Yoon Han, Mi Hee Lim, Hugh I. Kim

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Regulation of amyloid-β (Aβ) aggregation by metal ions and proteins is essential for understanding the pathology of Alzheimer's disease (AD). Human serum albumin (HSA), a regulator of metal and protein transportation, can modulate metal-Aβ interactions and Aβ aggregation in human fluid; however, the molecular mechanisms for such activities remain unclear. Herein, we report the molecular-level complexation between Zn(II), Cu(II), Aβ, and HSA, which is able to alter the aggregation and cytotoxicity of Aβ peptides and induce their cellular transportation. In addition, a single Aβ monomer-bound HSA is observed with the structural change of Aβ from a random coil to an α-helix. Small-angle X-ray scattering (SAXS) studies indicate that Aβ-HSA complexation causes no structural variation of HSA in solution. Conversely, ion mobility mass spectrometry (IM-MS) results present that Aβ prevents the shrinkage of the V-shaped groove of HSA in the gas phase. Consequently, for the first time, HSA is demonstrated to predominantly capture a single Aβ monomer at the groove using the phase transfer of a protein heterodimer from solution to the gas phase. Moreover, HSA sequesters Zn(II) and Cu(II) from Aβ while maintaining Aβ-HSA interaction. Therefore, HSA is capable of controlling metal-free and metal-bound Aβ aggregation and aiding the cellular transportation of Aβ via Aβ-HSA complexation. The overall results and observations regarding HSA, Aβ, and metal ions advance our knowledge of how protein-protein interactions associated with Aβ and metal ions could be linked to AD pathogenesis.

Original languageEnglish
Pages (from-to)15437-15445
Number of pages9
JournalJournal of the American Chemical Society
Volume139
Issue number43
DOIs
Publication statusPublished - 2017 Nov 1

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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