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

Bilal M. Qureshi, Andrea Schmidt, Elmar Behrmann, Jörg Bürger, Thorsten Mielke, Christian M. T. Spahn, Martin Heck, Patrick Scheerer

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12 Scopus citations


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
Original languageEnglish (US)
JournalNature Communications
Issue number1
StatePublished - Jan 8 2018

Bibliographical note

KAUST Repository Item: Exported on 2020-10-01
Acknowledgements: We thank Prof. Dr. Wolfgang Baehr (University of Utah, USA) for providing us PrBP/δ expression vector. We are obliged to Ms. Ingrid Semjonow, Ms. Helena Seibel and Mr. Brian Bauer for their excellent technical assistance in purifying reagents and in protein preparations. We are grateful to Uwe Müller, Manfred Weiss and the scientific staff of the BESSY-MX/Helmholtz Zentrum Berlin für Materialien und Energie at beamlines BL14.1, BL14.2 and BL14.3 operated by the Joint Berlin MX-Laboratory at the BESSY II electron storage ring (Berlin-Adlershof, Germany) and the scientific staff of the European Synchrotron Radiation Facility (ESRF, Grenoble) at beamlines ID14-1, ID14-4, ID23-1, ID23-2, ID30A, ID30B and ID29, where the data were collected, for continuous support. This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB740 to T.M., C.M.T.S, M.H., P.S.; SFB1078-B6 to P.S.; SFB958 to C.M.T.S.), DFG Cluster of Excellence ‘Unifying Concepts in Catalysis’ (Research Field D/E to P.S.). E.B. holds a Freigeist-Fellowship from the Volkswagen Foundation and acknowledges continuous support from the Caesar Foundation.


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