121st General Meeting of the KCS

Type Poster Presentation
Area Life Chemistry
Room No. Event Hall
Time 4월 20일 (금요일) 11:00~12:30
Code BIO.P-278
Subject Understanding the formation of amyloid fibrils and their cytotoxicity based on structural characterization of amyloid protein complexes
Authors Tae Su Choi
Department of Chemistry, Korea University, Korea
Abstract In this poster, I will present two amyloid protein complexes: α-synuclein (αSyn)–Cu(II) and human serum albumin(HSA)–amyloid-β (Aβ). αSyn, one of amyloid proteins related to Parkinson’s disease (PD), self-assemble to amyloid fibrils with morphologic variations. The morphology of αSyn fibrils has been suggested to play a significant role in cell-transmission and cytotoxicity of the fibrils. In particular, the short fibrils, physically disassembled by ultrasonication, have shown the enhanced neurotoxicity and cell-transmission. However, the formation mechanism of the short fibrils has been a challenging issue. I and my coworkers found that Cu(II), abundant in substantia nigra of human brain, induces the formation of short fibrils. Using small-angle X-ray scattering (SAXS) and ion mobility-mass spectrometry (IM-MS), we characterized the molecular interaction of αSyn monomer-Cu(II) complex. Consequently, the macrochelated conformation of the complex promotes the nucleation process of αSyn, but retards the elongation of αSyn fibrils. Our result indicates that Cu(II) modulate the formation mechanism of pathological αSyn fibrils. HSA, the most abundant protein in human plasma and brain, captures Aβ peptides, thereby preventing the formation of toxic aggregates. However, the molecular interaction of HSA–Aβ complex and its biological role have not been fully understood. Using SAXS and IM-MS, I and my coworkers found that HSA forms a 1:1 complex with Aβ, as well as Aβ is inserted to the groove region of HSA. In addition, this protein complex promotes the internalization of Aβ peptides from cell media to the cell interior. These results indicate that the molecular interaction with HSA plays a crucial role in the regulatory mechanism of Aβ aggregation in human brain.
E-mail choitaesu@korea.ac.kr