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Conformation of Y145Stop Prion Protein in Solution and Amyloid Fibrils Probed by Nuclear Magnetic Resonance Spectroscopy
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Conformation of Y145Stop Prion Protein in Solution and Amyloid Fibrils Probed by Nuclear Magnetic Resonance Spectroscopy. |
| 개인저자 | Xia, Yongjie. |
| 단체저자명 | The Ohio State University. Chemistry. |
| 발행사항 | [S.l.]: The Ohio State University., 2017. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2017. |
| 형태사항 | 142 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-05B. Dissertation Abstract International |
| ISBN | 9781687936929 |
| 학위논문주기 | Thesis (Ph.D.)--The Ohio State University, 2017. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-05, Section: B.
Advisor: Jaroniec, Christopher. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Nuclear magnetic resonance has become a popular biophysical technique to obtain the detailed structural information of biological macromolecules, which is important for understanding their functions. However, most NMR methods measuring the internuclear distance, such as the nuclear Overhauser effect (NOE), only allow the observation of distances shorter than 5 A, as the dipole-dipole couplings between nuclei become vanishingly small when distances exceed 5 A. The paramagnetic relaxation enhancement (PRE) method overcomes this problem and permits distance measurement up to 25~35 A by introducing an extrinsic paramagnetic center to the system, owing to the fact that the magnetic moment of an unpaired electron is much larger than that of a proton. In PRE method, the distance between the affected nucleus and the paramagnetic center is correlated with elevated relaxation rate. Therefore, long range distance information which is useful for structural analysis can be obtained from measured PRE values.The initial studies of this thesis, which is discussed in Chapter 2, present the 1H, 13C and 15N resonance assignments for three monomeric Y145Stop mammalian prion proteins (human, mouse and Syrian hamster) in solution, which are associated with a familial disease and are a valuable model for investigating the structural properties of amyloid strains and transmission barriers phenomena.1 By calculating the secondary chemical shifts of C慣, C棺 and CO values, it was found that the Y145Stop human, Syrian hamster and mouse PrP, corresponding to the N-terminus of full-length prion proteins, are highly disordered.In a subsequent series of studies described in Chapter 3, PRE effect was utilized to map the long range interactions in intrinsically disordered Y145Stop human prion protein under physiological conditions, which may be involved in the formation of early stage species possessing the ability to aggregate in the fibril formation process. Similar long distance contacts and radius of hydration were observed in human, Syrian hamster and mouse PrP23-144, which might be due to similar amino acid sequences.In Chapter 4, we investigate the intrinsic copper(II) binding site in huPrP23-144 by EPR spectroscopy and coupled PRE effects with solid state NMR spectroscopy to obtain the long range contacts between the flexible N-terminal tail and the rigid core region of huPrP23-144 in the fibrillar state. These results can be used as distance restraints to construct the conformational ensembles of the N-terminal domain. Interestingly, similar contacts were observed in huPrP23-144 in both physiological and fibrillar states.Finally, in Chapter 5, we present the studies of the residue-specific solvent accessibility in the core region of huPrP23-144 amyloid fibrils via PRE and hydrogen/deuterium exchange coupled with both solution and solid-state NMR spectroscopy. By comparing results from different experiments, a protection pattern in huPrP23-144 amyloid fibrils was found, in which residues 115 through 127 are buried inside a folded region. |
| 일반주제명 | Chemistry. Biochemistry. Biophysics. Physical chemistry. |
| 언어 | 영어 |
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