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thesis_Lu Yu-2015.pdf (3.87 MB)

ETD Abstract Container

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Structural Studies of Human Prion Proteins and Peptides

Yu, Lu
http://rave.ohiolink.edu/etdc/view?acc_num=case1447338491

Abstract Details

, Doctor of Philosophy, Case Western Reserve University, Biochemistry.
Prion diseases are unusual fatal neurodegenerative diseases, and their disease process involves pathogenic conformational change of the normal protein PrPC to the misfolded form PrPSc. Thus, structural characterization of the two forms of PrPs is essential to understand the disease mechanism. In our studies, we used X-ray crystallography as a tool to decipher several puzzling questions in the prion biology. Specifically, we solved structures of 11 peptides containing 6-7 residues spanning the ß1 strand with different polymorphic residues and revealed that M129 and V129 peptides always form different structures, which provides possible structural mechanism about the protective effects of M/V129 polymorphism in several human prion diseases. We also solved 3 prion protein structures: the G131V PrP structure revealed unique intra- and inter-molecular ß sheet conformation which may be important in PrPSc conversion; the R164A designed mutant resembles some of the disease mutants with intermolecular ß sheet formation, which agrees with our hypothesis about effects of the ß2-a2 loop; the species specific mutant S170N showed similar conformation as the WT PrP, which indicates that flexibility of the ß2-a2 loop might be more important in species barrier.
Vivien Yee (Advisor)
Menachem Shoham (Committee Chair)
Witold Surewicz (Committee Member)
Paul Carey (Committee Member)
Jun Qin (Committee Member)
Biochemistry

Recommended Citations

Citations

  • Yu, L. (n.d.). Structural Studies of Human Prion Proteins and Peptides [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1447338491

    APA Style (7th edition)

  • Yu, Lu. Structural Studies of Human Prion Proteins and Peptides. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1447338491.

    MLA Style (8th edition)

  • Yu, Lu. "Structural Studies of Human Prion Proteins and Peptides." Doctoral dissertation, Case Western Reserve University. Accessed MAY 21, 2024. http://rave.ohiolink.edu/etdc/view?acc_num=case1447338491

    Chicago Manual of Style (17th edition)

case1447338491
186
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This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.