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Mechanistic insights into the role of prenyl-binding protein PrBP/δ in membrane dissociation of phosphodiesterase 6

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  • Bilal M. Qureshi

    (Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    Group Protein X-ray Crystallography and Signal Transduction
    Group Cryo Electron Microscopy
    Group Enzyme Kinetics)

  • Andrea Schmidt

    (Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    Group Protein X-ray Crystallography and Signal Transduction)

  • Elmar Behrmann

    (Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    Group Cryo Electron Microscopy
    Center of Advanced European Studies and Research (Caesar)
    University of Cologne)

  • Jörg Bürger

    (Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    Group Cryo Electron Microscopy
    Max Planck Institute for Molecular Genetics)

  • Thorsten Mielke

    (Max Planck Institute for Molecular Genetics)

  • Christian M. T. Spahn

    (Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    Group Cryo Electron Microscopy)

  • Martin Heck

    (Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    Group Enzyme Kinetics)

  • Patrick Scheerer

    (Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health
    Group Protein X-ray Crystallography and Signal Transduction)

Abstract

Isoprenylated proteins are associated with membranes and their inter-compartmental distribution is regulated by solubilization factors, which incorporate lipid moieties in hydrophobic cavities and thereby facilitate free diffusion during trafficking. Here we report the crystal structure of a solubilization factor, the prenyl-binding protein (PrBP/δ), at 1.81 Å resolution in its ligand-free apo-form. Apo-PrBP/δ harbors a preshaped, deep hydrophobic cavity, capacitating apo-PrBP/δ to readily bind its prenylated cargo. To investigate the molecular mechanism of cargo solubilization we analyzed the PrBP/δ-induced membrane dissociation of rod photoreceptor phosphodiesterase (PDE6). The results suggest that PrBP/δ exclusively interacts with the soluble fraction of PDE6. Depletion of soluble species in turn leads to dissociation of membrane-bound PDE6, as both are in equilibrium. This “solubilization by depletion” mechanism of PrBP/δ differs from the extraction of prenylated proteins by the similar folded solubilization factor RhoGDI, which interacts with membrane bound cargo via an N-terminal structural element lacking in PrBP/δ.

Suggested Citation

  • Bilal M. Qureshi & Andrea Schmidt & Elmar Behrmann & Jörg Bürger & Thorsten Mielke & Christian M. T. Spahn & Martin Heck & Patrick Scheerer, 2018. "Mechanistic insights into the role of prenyl-binding protein PrBP/δ in membrane dissociation of phosphodiesterase 6," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-017-02569-y
    DOI: 10.1038/s41467-017-02569-y
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