E2~Ub conjugates regulate the kinase activity of Shigella effector OspG during pathogenesis. (20th January 2014)

• Record Type: Journal Article
• Authors: Pruneda, Jonathan N; Smith, F Donelson; Daurie, Angela; Swaney, Danielle L; Villén, Judit; Scott, John D; Stadnyk, Andrew W; Le Trong, Isolde; Stenkamp, Ronald E; Klevit, Rachel E; Rohde, John R; Brzovic, Peter S
• Is Part Of: EMBO journal. Volume 33:Number 5(2014)
• Page Start: 437
• Page End: 449
• Publication Date: 2014-01-20
• Subjects: Molecular biology -- Periodicals; 572.805
• DOI: 10.1002/embj.201386386
• Languages: English
• ISSNs: 0261-4189

Abstract

<abstract abstract-type="synopsis" xml:lang="en" id="embj201386386-abs-0002"> <title>Synopsis</title> <p> <boxed-text content-type="graphic" id="embj201386386-blkfxd-0001" position="anchor" orientation="portrait"> <graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg4sxhcxrd" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /> </boxed-text> </p> <p>The crystal structure of a complex between ubiquitin‐loaded UbcH5c and the <italic>Shigella</italic> effector kinase OspG shows how they regulate each other, and has allowed to demonstrate the role of this interaction in repressing host innate immune responses.</p> <p> <list id="embj201386386-list-0001" list-type="bullet"> <list-item> <p>Structure of the Shigella effector kinase OspG in complex with an activated UbcH5˜Ub conjugate reveals an unusual regulatory role for E2˜Ubs.</p> </list-item> <list-item> <p>OspG is a minimal kinase domain that requires binding to E2˜Ub conjugates to stimulate ATP binding and kinase activity.</p> </list-item> <list-item> <p>OspG can interact with a subset of related E2˜Ub conjugates.</p> </list-item> <list-item> <p>The structure of a stable UbcH5˜Ub conjugate in the OspG complex is compared to structures of UbcH5˜Ub poised for Ub transfer.</p> </list-item> <list-item> <p>Mouse models of Shigellosis show binding to host E2˜Ubs is required for OspG activity.</p> </list-item> </list> </p> </abstract>