• Login
    View Item 
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    •   Home
    • Theses and Dissertations
    • Theses and Dissertations
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Scholarly CommonsCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    About

    AboutCreative CommonsAugusta University LibrariesUSG Copyright Policy

    Statistics

    Display statistics

    AN INACTIVE RECEPTOR-G PROTEIN COMPLEX MAINTAINS THE DYNAMIC RANGE OF AGONIST-INDUCED SIGNALING

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Jang_gru_1907E_10241.pdf
    Size:
    1.953Mb
    Format:
    PDF
    Download
    Authors
    Jang, Wonjo
    URI
    http://hdl.handle.net/10675.2/624267
    
    Metadata
    Show full item record
    Abstract
    G protein-coupled receptors (GPCRs) are 7-transmembrane (TM) proteins that are targets of one-third of approved drugs. In response to agonist binding, GPCRs adopt active-state conformations that promote their association with G protein heterotrimers. The resulting active-state ternary complex (i.e., agonist-GPCR-G protein complex) is the basis for conventional stimulus-response coupling. However multiple studies have also described GPCR-G protein complexes that form prior to agonist binding. While others have previously proposed that this interaction is thought to promote rapid or specific signaling, the role of such “preassociated” complexes is not well understood, and inactive-state receptors are generally considered unable to interact with heterotrimeric G proteins. Here, we show that preassociation of 5-HT7 serotonin receptors with Gs heterotrimers is necessary for agonist-induced signaling. Because inverse agonists and receptor mutations that favor the inactive state of 5-HT7 receptors promote the formation of preassociated complexes, 5-HT7 receptors in their inactive state preassociate with Gs. Upon agonist binding, 5-HT7 receptors adopt conformations that disfavor the formation of inactive-state 5-HT7–Gs complexes, thus permitting the formation of conventional agonist–5-HT7–Gs ternary complexes. Because Gs variants that cannot form inactive-state 5-HT7-Gs complexes are constitutively activated by 5-HT7 receptors, we conclude that this unconventional inactive-state 5-HT7-Gs complex is critical for the dynamic range of agonist-induced signaling. Thus, our findings provide evidence that agonists can initiate signaling via two distinct mechanisms, by promoting the association of conventional ternary complexes and by disrupting inverse-coupled binary complexes.
    Affiliation
    Biomedical Sciences
    Collections
    Theses and Dissertations

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    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.