Events

CBE/ENGR 225 FACULTY SEMINAR: SONG-I HAN, PROFESSOR IN DEPARTMENT OF CHEMISTRY AND BIOCHEMISTRY & DEPT. OF CHEMICAL ENGINEERING, UCSB

Tuesday, March 29, 2016 at 4pm in Room ESB #2001

Song-I Han, Ph.D.

Professor in Department of Chemistry and Biochemistry

& Department of Chemical Engineering

 University of California, Santa Barbara

 

Tuesday, March 29, 2016

ESB 2001

4:00 pm – 5:00 pm

*coffee & cookies served*

 

Approaches to Unraveling Early Protein Aggregation Mechanisms

 

ABSTRACT:

Protein aggregation plays a critical role in the pathogenesis of neurodegenerative diseases, while the

mechanism of its progression is poorly understood. Several lines of evidence suggest that small

aggregated protein intermediates, that may constitute soluble oligomers and precede the formation of

highly structured fibrils, are primary toxic species contributing to the early on-set of

neurodegenerative diseases. However, studies of early intermediates are challenging, given the

transient nature and complex equilibria involving monomer and oligomer species. We employ sitespecific

measurements of surface water diffusion, protein segmental dynamics and inter-strand

packing to track early tau protein aggregation processes in situ. Tau is a microtubule-associated

protein that in its pathological form can dissociate from microtubules and aggregate to form insoluble

neurofibrillary tangles in neuronal cells. Our study reveals that tau aggregation is preceded by a

dramatic structural transformation within minutes of initiating aggregation, followed by the formation of

partially structured aggregation intermediates and their rearrangement into stable aggregate species

with beta-sheet signatures and fibrils. Once heparin is added to tau and an aggregation-prone

conformation of tau populated, the series of events leading up to fibrilization appear to be

energetically favorable "down-hill" processes. Our findings suggest that therapeutic intervention may

 

focus on disrupting the earliest aggregation events occurring in solution.