Qureshi, Bilal M., Schmidt, Andrea, Behrmann, Elmar ORCID: 0000-0001-6794-3669, Buerger, Joerg, Mielke, Thorsten, Spahn, Christian M. T., Heck, Martin and Scheerer, Patrick ORCID: 0000-0001-5028-2075 (2018). Mechanistic insights into the role of prenyl-binding protein PrBP/delta in membrane dissociation of phosphodiesterase 6. Nat. Commun., 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2041-1723

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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/delta), at 1.81 angstrom resolution in its ligand-free apo-form. Apo-PrBP/delta harbors a preshaped, deep hydrophobic cavity, capacitating apo-PrBP/delta to readily bind its prenylated cargo. To investigate the molecular mechanism of cargo solubilization we analyzed the PrBP/delta-induced membrane dissociation of rod photoreceptor phosphodiesterase (PDE6). The results suggest that PrBP/delta 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/delta 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/delta.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Qureshi, Bilal M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Behrmann, ElmarUNSPECIFIEDorcid.org/0000-0001-6794-3669UNSPECIFIED
Buerger, JoergUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mielke, ThorstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spahn, Christian M. T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heck, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Scheerer, PatrickUNSPECIFIEDorcid.org/0000-0001-5028-2075UNSPECIFIED
URN: urn:nbn:de:hbz:38-199052
DOI: 10.1038/s41467-017-02569-y
Journal or Publication Title: Nat. Commun.
Volume: 9
Date: 2018
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2041-1723
Language: English
Faculty: Faculty of Mathematics and Natural Sciences
Divisions: Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Biochemistry
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
ROD CGMP PHOSPHODIESTERASE; PDE-DELTA; INHIBITORY SUBUNIT; TRANSPORT; TRAFFICKING; SOLUBILIZATION; TRANSDUCIN; EFFECTOR; COMPLEX; DOMAINMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/19905

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