Skip to Main Content
Frequently Asked Questions
Submit an ETD
Global Search Box
Need Help?
Keyword Search
Participating Institutions
Advanced Search
School Logo
Files
File List
thesis of bo wu final.pdf (5.69 MB)
ETD Abstract Container
Abstract Header
Studies of Structure, Dynamics, and Interactions of Amyloid Fibrils by Magic Angle Spinning Solid State NMR
Author Info
Wu, Bo
Permalink:
http://rave.ohiolink.edu/etdc/view?acc_num=osu1365609635
Abstract Details
Year and Degree
2013, Doctor of Philosophy, Ohio State University, Chemistry.
Abstract
Amyloid fibrils are a large group of aggregates formed mainly by proteins and peptides. Lots of them are cytotoxic and causes of dozens of diseases, e.g. Alzheimer’s disease and Type II diabetes. Although the structures of amyloid fibrils contain important information of biochemistry and pathology of amyloid related disease, due to their insoluble nature, it is very difficult to study them by conventional structural methods, such as X-ray crystallography or solution NMR. Magic angle spinning (MAS) solid state NMR is a perfectly suitable method to study the amyloid fibrils, and is able to cover a very broad range of topics, from structures, dynamics to interactions. The theme of this thesis focuses on various topics related to amyloid fibrils by MAS solid state NMR methods, and tries to improve our understanding of the fundamentals of amyloid fibrils. The thesis is organized as follows: In Chapter 2, we analyzed the effects of deletion of an important core sequence in PrP (23-144) protein on the structures and organizations of the amyloid fibrils: We obtained the resonance assignments by a set of 2D and 3D solid state NMR experiments, and analyzed and compared the secondary structures of WT and deletion mutants. In Chapter 3, we designed a new approach to study the intermolecular dynamics of amyloid fibrils by an Alzheimer’s ß peptides, Aß40. By using a double quantum filter dipolar recoupling method and specific labeling, we were able to detect the recycling within the amyloid fibrils directly for the first time with a solid state NMR method. Our observations encouraged us to analyze the effects of different recycling models on the results of different approaches, and shed light to the mechanisms of amyloid formation kinetics. In Chapter 4, we studied the interactions between an important molecules bound to amyloid fibrils, Congo red and amyloid fibrils formed by a segment of transtherytin (TTR) (105-115). With 1D and 2D solid state NMR methods, we identified the significant chemical shift perturbations, and probably binding sites. We preliminarily concluded that the Congo red molecules bound to TTR (105-115) at the two ends. In Chapter 5, we performed a proof of principle experiment to study the interactions between another important molecules bound to amyloid fibrils, thioflavin T and microcrystalline precipitate formed by an amyloid related protein, ß2-microglobulin. In both solution and solid state NMR studies, we identified significant and specific chemical shift perturbations, agreeing well with previous crystallography studies.
Committee
Chris Jaroniec, Ph.D (Advisor)
Tom Magliery, Ph.D (Committee Member)
Philip Grandinetti, Ph.D (Committee Member)
Pages
182 p.
Subject Headings
Biochemistry
;
Biophysics
;
Chemistry
Recommended Citations
Refworks
EndNote
RIS
Mendeley
Citations
Wu, B. (2013).
Studies of Structure, Dynamics, and Interactions of Amyloid Fibrils by Magic Angle Spinning Solid State NMR
[Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1365609635
APA Style (7th edition)
Wu, Bo.
Studies of Structure, Dynamics, and Interactions of Amyloid Fibrils by Magic Angle Spinning Solid State NMR.
2013. Ohio State University, Doctoral dissertation.
OhioLINK Electronic Theses and Dissertations Center
, http://rave.ohiolink.edu/etdc/view?acc_num=osu1365609635.
MLA Style (8th edition)
Wu, Bo. "Studies of Structure, Dynamics, and Interactions of Amyloid Fibrils by Magic Angle Spinning Solid State NMR." Doctoral dissertation, Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1365609635
Chicago Manual of Style (17th edition)
Abstract Footer
Document number:
osu1365609635
Download Count:
634
Copyright Info
© 2013, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.