Shared more. Cited more. Safe forever.
    • advanced search
    • submit works
    • about
    • help
    • contact us
    • login
    View Item 
    •   MOspace Home
    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2005 Dissertations (MU)
    • 2005 MU dissertations - Access restricted to UM
    • View Item
    •   MOspace Home
    • University of Missouri-Columbia
    • Graduate School - MU Theses and Dissertations (MU)
    • Theses and Dissertations (MU)
    • Dissertations (MU)
    • 2005 Dissertations (MU)
    • 2005 MU dissertations - Access restricted to UM
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.
    advanced searchsubmit worksabouthelpcontact us

    Browse

    All of MOspaceCommunities & CollectionsDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis SemesterThis CollectionDate IssuedAuthor/ContributorTitleIdentifierThesis DepartmentThesis AdvisorThesis Semester

    Statistics

    Most Popular ItemsStatistics by CountryMost Popular AuthorsStatistics by Referrer

    Crystal structure of the kelch domain of human keap1

    Li, Xuchu, 1976-
    View/Open
    [PDF] public.pdf (42.97Kb)
    [PDF] short.pdf (11.90Kb)
    [PDF] research.pdf (1.690Mb)
    Date
    2005
    Format
    Thesis
    Metadata
    [+] Show full item record
    Abstract
    [ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Nrf2-Keap1 signal transduction pathway senses oxidative stress and protects eukaryotic cells against oxidative damage and cancer. The transcription factor Nrf2 induces Phase II stress response genes, which enable cells to neutralize reactive molecules and restore cellular redox homeostasis. Keap1 is a BTBKelch protein that regulates both the subcellular localization and steady state levels of Nrf2. Recently our lab has identified Keap1 as a redox-regulated substrate adaptor protein for a Cullin3-dependent E3 ubiquitin ligase complex, which targets Nrf2 for degradation in a controlled manner. The research project presented in this dissertation is to study the interaction between Nrf2 and Keap1 starting from a structural biology approach. The N-terminal Neh2 domain of Nrf2 mediates binding of Nrf2 to the Kelch domain of Keap1. We solved the crystal structure of the Kelch domain of human Keap1 and carried out detailed analysis of the structural/solvent features in this domain. This domain structure, which was the first high-resolution structure of a mammalian Kelch domain, demonstrated that the Kelch domain of Keap1 is a six-bladed ?-propeller that uses a C-terminal mode of closure. The structure revealed how conserved amino acids and water molecules contribute to both inter- and intra-blade stability and provided insight into how disease-causing mutations perturb the structural integrity of the Kelch domain. We found that the bottom loops of the Kelch domain are critical for its sufficient association with the Neh2 domain. Based on mutagenesis data, we mapped out a Neh2-Kelch interface on the bottom side of the Kelch domain. We further crystallized a putative Kelch-Neh2 complex that diffracts to 4[angstrom]. We are now in the process of obtaining high quality crystals of the Neh2-Kelch complex for structure determination purpose.--From public.pdf
    URI
    https://hdl.handle.net/10355/5828
    https://doi.org/10.32469/10355/5828
    Degree
    Ph. D.
    Thesis Department
    Biochemistry (MU)
    Rights
    Access to files is limited to the campuses of the University of Missouri.
    Collections
    • 2005 MU dissertations - Access restricted to UM
    • Biochemistry electronic theses and dissertations (MU)
    • Biochemistry electronic theses and dissertations (MU)

    Send Feedback
    hosted by University of Missouri Library Systems
     

     


    Send Feedback
    hosted by University of Missouri Library Systems