Structural highlights
FunctionPDE6D_HUMAN Acts as a GTP specific dissociation inhibitor (GDI). Increases the affinity of ARL3 for GTP by several orders of magnitude and does so by decreasing the nucleotide dissociation rate. Stabilizes Arl3-GTP by decreasing the nucleotide dissociation (By similarity). Publication Abstract from PubMedDefects in primary cilia result in human diseases known as ciliopathies. The retinitis pigmentosa GTPase regulator (RPGR), mutated in the most severe form of the eye disease, is located at the transition zone of the ciliary organelle. The RPGR-interacting partner PDEdelta is involved in trafficking of farnesylated ciliary cargo, but the significance of this interaction is unknown. The crystal structure of the propeller domain of RPGR shows the location of patient mutations and how they perturb the structure. The RPGR.PDEdelta complex structure shows PDEdelta on a highly conserved surface patch of RPGR. Biochemical experiments and structural considerations show that RPGR can bind with high affinity to cargo-loaded PDEdelta and exposes the Arl2/Arl3-binding site on PDEdelta. On the basis of these results, we propose a model where RPGR is acting as a scaffold protein recruiting cargo-loaded PDEdelta and Arl3 to release lipidated cargo into cilia. The interplay between RPGR, PDEdelta and Arl2/3 regulate the ciliary targeting of farnesylated cargo.,Watzlich D, Vetter I, Gotthardt K, Miertzschke M, Chen YX, Wittinghofer A, Ismail S EMBO Rep. 2013 Apr 5. doi: 10.1038/embor.2013.37. PMID:23559067[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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