Page 14 - T. Protein modification and regulation

[T. Protein modification and regulation-7]

Core sequence of Tau regulating its aggregation process

Jeeyoung Lee¹, Ly Thi Huong Luu Le¹, Min Jae Lee¹

¹Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080,

Korea

In tauopathies, the microtubule-associated protein tau (Tau) is abnormally aggregated and forms neurofibrillary
tangles (NFTs). A recent study using human AD brains revealed the core sequence (Tau core) of the ordered β-sheet

structure. Among the four microtubule-binding repeat domains (MTBRs) in the full-length Tau (Tau FL), the Tau core

consists of V306 to F378 of Tau FL, spanning MTBRs 3 and 4. To examine whether the protofilament core sequence
affects the aggregation process of Tau FL, we purified the recombinant Tau core protein and raised its targeting
antibodies. Our in vitro oligomerization assay, electron microscopic analysis, and dot blot assay indicated that Tau

Core facilitates Tau aggregation even in the absence of heparin, which is more physiologically relevant. Therefore,
Tau Core appears to be critical in the formation of tau filaments in human brain and can be used an important tool

for Tau study. Biophysical analysis using Tau Core is in progress to verify its aggregation kinetics.