• Login
    View Item 
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    •   Home
    • The Manchester Institute Cancer Research UK
    • All Paterson Institute for Cancer Research
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Disease-associated sequence variations congregate in a polyanion recognition patch on human factor H revealed in three-dimensional structure.

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Authors
    Herbert, A
    Uhrín, D
    Lyon, Malcolm
    Pangburn, M
    Barlow, P
    Affiliation
    Edinburgh Biomolecular NMR Unit, University of Edinburgh, West mains Road, Edinburgh EH9 3JJ, United Kingdom.
    Issue Date
    2006-06-16
    
    Metadata
    Show full item record
    Abstract
    Mutations and polymorphisms in the regulator of complement activation, factor H, have been linked to atypical hemolytic uremic syndrome (aHUS), membranoproliferative glomerulonephritis, and age-related macular degeneration. Many aHUS patients carry mutations in the two C-terminal modules of factor H, which normally confer upon this abundant 155-kDa plasma glycoprotein its ability to selectively bind self-surfaces and prevent them from inappropriately triggering the complement cascade via the alternative pathway. In the current study, the three-dimensional solution structure of the C-terminal module pair of factor H has been determined. A binding site for a fully sulfated heparin-derived tetrasaccharide has been delineated using chemical shift mapping and the C3d/C3b-binding site inferred from sequence comparisons and computational docking. The resultant information allows assessment of the likely consequences of aHUS-associated amino acid substitutions in this critical region of factor H. It is striking that, excepting those likely to perturb the three-dimensional structure, aHUS-associated missense mutations congregate in the polyanion-binding site delineated in this study, thus potentially disrupting a vital mechanism for control of complement on self-surfaces in the microvasculature of the kidney. It is intriguing that a single nucleotide polymorphism predisposing to age-related macular degeneration occupies another region of factor H that harbors a polyanion-binding site.
    Citation
    Disease-associated sequence variations congregate in a polyanion recognition patch on human factor H revealed in three-dimensional structure. 2006, 281 (24):16512-20 J. Biol. Chem.
    Journal
    The Journal of Biological Chemistry
    URI
    http://hdl.handle.net/10541/72696
    DOI
    10.1074/jbc.M513611200
    PubMed ID
    16533809
    Type
    Article
    Language
    en
    ISSN
    0021-9258
    ae974a485f413a2113503eed53cd6c53
    10.1074/jbc.M513611200
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

    entitlement

    Related articles

    • Mutations of factor H impair regulation of surface-bound C3b by three mechanisms in atypical hemolytic uremic syndrome.
    • Authors: Lehtinen MJ, Rops AL, Isenman DE, van der Vlag J, Jokiranta TS
    • Issue date: 2009 Jun 5
    • Structural and functional characterization of the product of disease-related factor H gene conversion.
    • Authors: Herbert AP, Kavanagh D, Johansson C, Morgan HP, Blaum BS, Hannan JP, Barlow PN, Uhrín D
    • Issue date: 2012 Mar 6
    • Translational mini-review series on complement factor H: structural and functional correlations for factor H.
    • Authors: Schmidt CQ, Herbert AP, Hocking HG, Uhrín D, Barlow PN
    • Issue date: 2008 Jan
    • Disease-linked mutations in factor H reveal pivotal role of cofactor activity in self-surface-selective regulation of complement activation.
    • Authors: Kerr H, Wong E, Makou E, Yang Y, Marchbank K, Kavanagh D, Richards A, Herbert AP, Barlow PN
    • Issue date: 2017 Aug 11
    • Complement C3b/C3d and cell surface polyanions are recognized by overlapping binding sites on the most carboxyl-terminal domain of complement factor H.
    • Authors: Hellwage J, Jokiranta TS, Friese MA, Wolk TU, Kampen E, Zipfel PF, Meri S
    • Issue date: 2002 Dec 15
    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.