• Login
    View Item 
    •   Home
    • Research from April 2016
    • Biomedical and biological science
    • View Item
    •   Home
    • Research from April 2016
    • Biomedical and biological science
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UOBREPCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalDepartmentThis CollectionTitleAuthorsIssue DateSubmit DateSubjectsPublisherJournalDepartment

    My Account

    LoginRegister

    About

    AboutLearning ResourcesResearch Graduate SchoolResearch InstitutesUniversity Website

    Statistics

    Display statistics

    Zinc-induced oligomerisation of zinc α2 glycoprotein reveals multiple fatty acid binding sites

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Zahid, Henna
    Miah, Layeque
    Lau, Andy M.
    Brochard, Lea
    Hati, Debolina
    Bui, Tam T. T.
    Drake, Alex F.
    Gor, Jayesh
    Perkins, Stephen J.
    McDermott, Lindsay C.
    Affiliation
    King's College London
    University College London
    University of Bedfordshire
    Issue Date
    2015-12-09
    Subjects
    adiposity
    zinc
    
    Metadata
    Show full item record
    Other Titles
    Zinc-induced oligomerization of zinc α2 glycoprotein
    Abstract
    Zinc α2 glycoprotein (ZAG) is an adipokine with a class I major histocompatibility complex protein fold and is associated with obesity and diabetes. Although its intrinsic ligand remains unknown, ZAG binds the dansylated C11 fatty acid, DAUDA, in the groove between the α1 and α2 domains. The surface of ZAG has about 15 weak zinc binding sites deemed responsible for precipitation from human plasma. Here the functional significance of these metal sites was investigated. Analytical ultracentrifugation and circular dichroism showed that zinc, but not other divalent metals, cause ZAG to oligomerise in solution. Thus ZAG dimers and trimers were observed in the presence of 1 mM and 2 mM zinc. Molecular modelling of X-ray scattering curves and sedimentation coefficients indicated a progressive stacking of ZAG monomers, suggesting the ZAG groove may be occluded in these. Using fluorescence-detected sedimentation velocity, these ZAG-zinc oligomers were again observed in the presence of the fluorescent boron dipyrromethene fatty acid C16-BODIPY. Fluorescence spectroscopy confirmed that ZAG binds C16-BODIPY. ZAG binding to C16-BODIPY, but not to DAUDA, was reduced by increased zinc concentrations. We conclude that the lipid binding groove in ZAG contains at least two distinct fatty acid binding sites for DAUDA and C16-BODIPY, similar to the multiple lipid binding seen in the structurally-related immune protein Cd1c. In addition, because high concentrations of zinc occur in the pancreas, the perturbation of these multiple lipid binding sites by zinc may be significant in Type 2 diabetes where dysregulation of ZAG and zinc homeostasis occurs.
    Citation
    Zahid H, Miah L, Lau AM, Brochard L, Hati D, Bui TTT, Drake AF, Gor J, Perkins SJ, McDermott LC (2015) 'Zinc-induced oligomerisation of zinc α2 glycoprotein reveals multiple fatty acid binding sites', Biochemical Journal, 473, pp.43-54.
    Publisher
    Portland Press
    Journal
    Biochemical Journal
    URI
    http://hdl.handle.net/10547/622302
    DOI
    doi:10.1042/BJ20150836
    Additional Links
    http://www.biochemj.org/content/473/1/43.article-info
    Type
    Article
    Language
    en
    ISSN
    0264-6021
    Sponsors
    This work was supported by the Collaborative Computational Project for advanced analyses of structural data in chemical biology and soft condensed matter (CCPSAS), a joint Engineering and Physical Sciences Research Council (EPSRC) [grant number EP/K039121/1]; and the National Science Foundation (NSF) [grant number CHE- 1265821].
    ae974a485f413a2113503eed53cd6c53
    doi:10.1042/BJ20150836
    Scopus Count
    Collections
    Biomedical and biological science

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  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.