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

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

Probing Distinct Fullerene Formation Processes from Carbon Precursors of Different Sizes and Structures

Fullerenes, cage-structured carbon allotropes, have been the subject of extensive research as new materials for diverse purposes. Yet, their formation process is still not clearly understood at the molecular level. In this study, we performed laser desorption ionization-ion mobility-mass spectrometry (LDI-IM-MS) of carbon substrates possessing different molecular sizes and structures to understand the formation process of fullerene. Our observations show that the formation process is strongly dependent on the size of the precursor used, with small precursors yielding small fullerenes and large graphitic precursors generally yielding larger fullerenes. These results clearly demonstrate that fullerene formation can proceed via both bottom-up and top-down processes, with the latter being favored for large precursors and more efficient at forming fullerenes. Furthermore, we observed that specific structures of carbon precursors could additionally affect the relative abundance of C₆₀ fullerene. Overall, this study provides an advanced understanding of the mechanistic details underlying the formation processes of fullerene