Fold and function of polypeptide transport-associated domains responsible for delivering unfolded proteins to membranes

Timothy J. Knowles, Mark Jeeves, Saeeda Bobat, Felician Dancea, Darren McClelland, Tracy Palmer, Michael Overduin, Ian R. Henderson

    Research output: Contribution to journalArticle

    116 Citations (Scopus)

    Abstract

    Membranes of Gram-negative bacteria, mitochondria and chloroplasts receive and fold beta-barrel transmembrane proteins through the action of polypeptide transport-associated (POTRA) domains. In Escherichia coli, folding substrates are inserted into the outer membrane by the essential protein YaeT, a prototypic Omp85 protein. Here, the articulation between tandem POTRA domains in solution is defined by nuclear magnetic resonance (NMR) spectroscopy, indicating an unprecedented juxtaposition. The novel solution orientations of all five POTRA domains are revealed by small-angle X-ray scattering of the entire 46 kDa periplasmic region. NMR titration studies show that strands from YaeT's canonical folding substrate, PhoE, bind non-specifically along alternating sides of its mixed beta sheets, thus providing an ideal platform for helping to fold nascent outer-membrane proteins. Together, this provides the first structural model of how multiple POTRA domains recruit substrates from the periplasmic solution into the outer membrane.

    Original languageEnglish
    Pages (from-to)1216-1227
    Number of pages12
    JournalMolecular Microbiology
    Volume68
    Issue number5
    DOIs
    Publication statusPublished - Jun 2008

    Keywords

    • OUTER-MEMBRANE
    • ESCHERICHIA-COLI
    • SOLUTION SCATTERING
    • BIOLOGICAL MACROMOLECULES
    • YAET COMPLEX
    • BIOGENESIS
    • SYSTEM
    • IDENTIFICATION
    • COMPONENT
    • PROGRAM

    Cite this

    Knowles, Timothy J. ; Jeeves, Mark ; Bobat, Saeeda ; Dancea, Felician ; McClelland, Darren ; Palmer, Tracy ; Overduin, Michael ; Henderson, Ian R. / Fold and function of polypeptide transport-associated domains responsible for delivering unfolded proteins to membranes. In: Molecular Microbiology. 2008 ; Vol. 68, No. 5. pp. 1216-1227.
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    abstract = "Membranes of Gram-negative bacteria, mitochondria and chloroplasts receive and fold beta-barrel transmembrane proteins through the action of polypeptide transport-associated (POTRA) domains. In Escherichia coli, folding substrates are inserted into the outer membrane by the essential protein YaeT, a prototypic Omp85 protein. Here, the articulation between tandem POTRA domains in solution is defined by nuclear magnetic resonance (NMR) spectroscopy, indicating an unprecedented juxtaposition. The novel solution orientations of all five POTRA domains are revealed by small-angle X-ray scattering of the entire 46 kDa periplasmic region. NMR titration studies show that strands from YaeT's canonical folding substrate, PhoE, bind non-specifically along alternating sides of its mixed beta sheets, thus providing an ideal platform for helping to fold nascent outer-membrane proteins. Together, this provides the first structural model of how multiple POTRA domains recruit substrates from the periplasmic solution into the outer membrane.",
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    Fold and function of polypeptide transport-associated domains responsible for delivering unfolded proteins to membranes. / Knowles, Timothy J.; Jeeves, Mark; Bobat, Saeeda; Dancea, Felician; McClelland, Darren; Palmer, Tracy; Overduin, Michael; Henderson, Ian R.

    In: Molecular Microbiology, Vol. 68, No. 5, 06.2008, p. 1216-1227.

    Research output: Contribution to journalArticle

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    AU - Knowles, Timothy J.

    AU - Jeeves, Mark

    AU - Bobat, Saeeda

    AU - Dancea, Felician

    AU - McClelland, Darren

    AU - Palmer, Tracy

    AU - Overduin, Michael

    AU - Henderson, Ian R.

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