5t4x | pdb_00005t4x

CRYSTAL STRUCTURE OF PDE6D IN APO-STATE

Structural highlights

5t4x is a 1 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Pde6d (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PDE6D_MOUSE] Promotes the release of prenylated target proteins from cellular membranes (PubMed:22179043). Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location (PubMed:22179043). Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E (By similarity). Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI) (PubMed:22179043). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate.[UniProtKB:O43924][UniProtKB:Q95142]^[1] ^[2] ^[3]

Publication Abstract from PubMed

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 A 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.

Mechanistic insights into the role of prenyl-binding protein PrBP/delta in membrane dissociation of phosphodiesterase 6.,Qureshi BM, Schmidt A, Behrmann E, Burger J, Mielke T, Spahn CMT, Heck M, Scheerer P Nat Commun. 2018 Jan 8;9(1):90. doi: 10.1038/s41467-017-02569-y. PMID:29311697^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Linari M, Hanzal-Bayer M, Becker J. The delta subunit of rod specific cyclic GMP phosphodiesterase, PDE delta, interacts with the Arf-like protein Arl3 in a GTP specific manner. FEBS Lett. 1999 Sep 10;458(1):55-9. PMID:10518933
↑ Hanzal-Bayer M, Linari M, Wittinghofer A. Properties of the interaction of Arf-like protein 2 with PDEdelta. J Mol Biol. 2005 Jul 29;350(5):1074-82. PMID:15979089 doi:10.1016/j.jmb.2005.05.036
↑ Chandra A, Grecco HE, Pisupati V, Perera D, Cassidy L, Skoulidis F, Ismail SA, Hedberg C, Hanzal-Bayer M, Venkitaraman AR, Wittinghofer A, Bastiaens PI. The GDI-like solubilizing factor PDEdelta sustains the spatial organization and signalling of Ras family proteins. Nat Cell Biol. 2011 Dec 18;14(2):148-58. doi: 10.1038/ncb2394. PMID:22179043 doi:https://dx.doi.org/10.1038/ncb2394
↑ Qureshi BM, Schmidt A, Behrmann E, Burger J, Mielke T, Spahn CMT, Heck M, Scheerer P. Mechanistic insights into the role of prenyl-binding protein PrBP/delta in membrane dissociation of phosphodiesterase 6. Nat Commun. 2018 Jan 8;9(1):90. doi: 10.1038/s41467-017-02569-y. PMID:29311697 doi:https://dx.doi.org/10.1038/s41467-017-02569-y

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OCA

[1] Linari M, Hanzal-Bayer M, Becker J. The delta subunit of rod specific cyclic GMP phosphodiesterase, PDE delta, interacts with the Arf-like protein Arl3 in a GTP specific manner. FEBS Lett. 1999 Sep 10;458(1):55-9. PMID:10518933

[2] Hanzal-Bayer M, Linari M, Wittinghofer A. Properties of the interaction of Arf-like protein 2 with PDEdelta. J Mol Biol. 2005 Jul 29;350(5):1074-82. PMID:15979089 doi:10.1016/j.jmb.2005.05.036

[3] Chandra A, Grecco HE, Pisupati V, Perera D, Cassidy L, Skoulidis F, Ismail SA, Hedberg C, Hanzal-Bayer M, Venkitaraman AR, Wittinghofer A, Bastiaens PI. The GDI-like solubilizing factor PDEdelta sustains the spatial organization and signalling of Ras family proteins. Nat Cell Biol. 2011 Dec 18;14(2):148-58. doi: 10.1038/ncb2394. PMID:22179043 doi:https://dx.doi.org/10.1038/ncb2394

[4] Qureshi BM, Schmidt A, Behrmann E, Burger J, Mielke T, Spahn CMT, Heck M, Scheerer P. Mechanistic insights into the role of prenyl-binding protein PrBP/delta in membrane dissociation of phosphodiesterase 6. Nat Commun. 2018 Jan 8;9(1):90. doi: 10.1038/s41467-017-02569-y. PMID:29311697 doi:https://dx.doi.org/10.1038/s41467-017-02569-y

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[2]

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[4]

5t4x | pdb_00005t4x

CRYSTAL STRUCTURE OF PDE6D IN APO-STATE

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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