Texas A&M University LibrariesTexas A&M University LibrariesTexas A&M University Libraries
    • Help
    • Login
    OAKTrust
    View Item 
    •   OAKTrust Home
    • Programs, Centers, and Institutes
    • Undergraduate Research and Capstones
    • Undergraduate Research Scholars Capstone (2006–present)
    • View Item
    •   OAKTrust Home
    • Programs, Centers, and Institutes
    • Undergraduate Research and Capstones
    • Undergraduate Research Scholars Capstone (2006–present)
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Deciphering the Effect of Nemaline-Myopathy Nebulin Mutations on Desmin Binding

    Thumbnail
    View/Open
    Jacobs.pdf (5.502Mb)
    Date
    2012-07-11
    Author
    Jacobs, Krystyna M
    Metadata
    Show full item record

    Abstract
    Our research focuses on the role of intermediate proteins in human disease. Desmin, a major intermediate filament protein in muscle cells, is organized into a central coiledcoil alpha helical domain flanked by globular head and tail domains. Our goal is to decipher the functional significance of the association of desmin to the giant thin filament protein nebulin at the sarcomeric Z-discs and its relation to muscle disease. Mutations in nebulin cause nemaline myopathy, a debilitating genetic muscle disease that affects children and adults alike. Previous research has shown that nebulin has a high affinity binding to desmin. However, little is known about the contribution of lower affinity binding desmin domains to nebulin or about the involvement of this interaction in nemaline myopathy. We hypothesize that the desmin 3-dimensional linkage to nebulin contributes to nemaline myopathy pathology. To test our hypothesis, we tested the binding profile of a nebulin-associated nemaline myopathy mutation to particular desmin domains using biochemical approaches. Our ELISA and GST-pull down assays showed that nebulin modules 160-164 bind to desmin?s central rod coil 2b and tail subdomains. Moreover, we found significantly decreased binding of the desmin coil 2b to the nemaline myopathy Nebulin M160-164 T5681P mutant as compared to nebulin M160-164. A 3-fold binding increase of the coil 2b was found in random alanine nebulin M160-164 L5646A mutant as compared to nebulin nemaline-associated nebulin M160-164 T5681P mutant, underscoring the importance of this region to the interaction of desmin and nebulin. Taken together, our findings suggest that differences in the binding profile of nemaline-associated nebulin mutations to desmin may contribute to our understanding the underlying molecular mechanism responsible for this disease. This knowledge may be significant because it may aid in devising new treatments for nemaline myopathy patients in the future.
    URI
    http://hdl.handle.net/1969.1/ETD-TAMU-2010-05-8115
    http://hdl.handle.net/1969.1/148748
    Subject
    Nebulin
    Desmin
    Nebulin M160-164
    T5681P
    L5646A
    Nemalin Myopathy mutations
    intermediate filaments, sarcomere, striated muscle
    Collections
    • Undergraduate Research Scholars Capstone (2006–present)
    Citation
    Jacobs, Krystyna M (2010). Deciphering the Effect of Nemaline-Myopathy Nebulin Mutations on Desmin Binding. Honors and Undergraduate Research. Available electronically from http : / /hdl .handle .net /1969 .1 /ETD -TAMU -2010 -05 -8115.

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Advanced Search

    Browse

    All of OAKTrustCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsDepartmentThis CollectionBy Issue DateAuthorsTitlesSubjectsDepartment

    My Account

    LoginRegister

    Statistics

    View Usage Statistics
    Help and Documentation

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV