[2P-2] Poster 2 (2P-38ー2P-88)

[2P-53*] Early aggregation kinetics preceding the nucleation in distinct amyloid formation pathways between bovine and human insulin

^○Keisuke Yuzu¹, Hiroshi Imamura², Takuro Nozaki¹, Ken Morishima³, Aya Okuda³, Rintaro Inoue³, Masaaki Sugiyama³, Eri Chatani¹ (1.Grad. Sch. Sci., Kobe Univ., 2.Coll. Life Sci., Ritsumeikan Univ., 3.KURNS, Kyoto Univ.)

Amyloid fibrils are a form of protein aggregates that are associated with serious amyloidoses and neurodegenerative diseases. Amyloid formation is typically progressed through nucleation and growth phases, and the nucleation phase is a rate-limiting step. Once amyloid nuclei are formed, the subsequent elongation of amyloid fibrils is promptly induced. Therefore, the nucleation process is considered as a key molecular event that dictates the amyloid formation. However, much remains unknown how the amyloid nucleation occurs.
We previously showed that bovine insulin formed prefibrillar intermediates in an early reaction phase, representing a characteristic association behavior during the nucleation. Herein, we investigated the early aggregation mechanism using bovine and human insulin, the amyloid structures of which are different. As a result of dynamic and static light scattering measurements, distinct evolution patterns of aggregates were observed between the two types of insulin; bovine insulin showed rapid development with a monodisperse distribution, in contrast to slow association of human insulin. Based on further analyses, detailed aggregation mechanisms of both insulin molecules preceding the nucleation will be discussed.