• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    The Allostery and Specificity of EF Hand Calcium-Binding Proteins

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Young_umaryland_0373D_11392.pdf
    Size:
    48.72Mb
    Format:
    PDF
    Download
    Author
    Young, Brianna cc
    Advisor
    Weber, David J., Ph.D.
    Date
    2022
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    EF-hand Ca2+-binding proteins (CBPs), such as calmodulin (CaM) or those belonging to the S100 protein family (S100s) undergo conformational changes upon increasing intracellular Ca2+, facilitating interactions with protein targets and inducing important biological responses. In the absence of target, the Ca2+-binding affinity of CaM and most S100 proteins is weak (CaKD >1 μM). However, when bound to effectors, allosteric mechanisms increase the Ca2+ affinity of these CBPs (CaKD <1 μM) to allow for proper Ca2+ homeostasis and maintenance of Ca2+-signaling. The Ca2+-tightening of these CBPs is described here by the “binding and functional folding” framework for detailing this physiologically relevant phenomenon. This research seeks to elucidate both the mechanisms of allostery and the basis of ligand- and target- specificity for S100 proteins and CaM. First, molecular fragments were used to differentiate between two highly similar S100 proteins, S100B and S100A1, with the goal of designing S100-specific inhibitors to block these elevated S100 proteins in various disease states. This provided insight into the specificity of S100A1 versus S100B for small molecules and will enable improved S100 protein-based drug design efforts. S100A1 and S100B binding to ions was also compared and differences between ion binding sites within the two highly similar proteins were determined. Another study revealed an allosteric mechanism in which a peptide termed BP2, derived from the STRA6 vitamin A transporter, increased the Ca2+-binding affinity of CaM upon binding. CaM-STRA6 complex formation was observed at physiologically relevant free Ca2+ concentrations (<1 μM), suggesting that retinol transport by full-length CaCaM-STRA6 may be regulated by Ca2+-signaling. The effect of CaM on multiple full-length target proteins was then discussed to further describe CaM allostery. Together, these studies lead to an improved understanding of Ca2+ signaling, CBP allostery and CBP-target- and ligand- interaction specificity.
    Description
    University of Maryland, Baltimore. Biochemistry. Ph.D. 2022.
    Keyword
    S100
    Calcium
    Calmodulin
    EF Hand Motifs
    Magnetic Resonance Spectroscopy
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/20356
    Collections
    Theses and Dissertations School of Medicine
    Theses and Dissertations All Schools

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.