4JHP

The crystal structure of the RPGR RCC1-like domain in complex with PDE6D

Summary for 4JHP

• Entry DOI: 10.2210/pdb4jhp/pdb
• Related: 4JHN
• Descriptor: Retinal rod rhodopsin-sensitive cGMP 3',5'-cyclic phosphodiesterase subunit delta, X-linked retinitis pigmentosa GTPase regulator (3 entities in total)
• Functional Keywords: immunoglobulin-like beta-sandwich, rcc1-like domain, beta propellar, seven bladed-propeller, structural protein, lipid binding protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm, cytoskeleton, flagellum axoneme (By similarity). Isoform 6: Cytoplasm, cytoskeleton, centrosome: Q92834
• Total number of polymer chains: 2
• Total formula weight: 60125.95

Authors

Waetzlich, D.,Vetter, I.,Wittinghofer, A.,Ismail, S. (deposition date: 2013-03-05, release date: 2013-04-17, Last modification date: 2023-09-20)

Primary citation

Watzlich, D.,Vetter, I.,Gotthardt, K.,Miertzschke, M.,Chen, Y.X.,Wittinghofer, A.,Ismail, S.
The interplay between RPGR, PDE-delta and Arl2/3 regulate the ciliary targeting of farnesylated cargo.
Embo Rep., 14:465-472, 2013

PubMed Abstract: Defects 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 PDEδ 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·PDEδ complex structure shows PDEδ on a highly conserved surface patch of RPGR. Biochemical experiments and structural considerations show that RPGR can bind with high affinity to cargo-loaded PDEδ and exposes the Arl2/Arl3-binding site on PDEδ. On the basis of these results, we propose a model where RPGR is acting as a scaffold protein recruiting cargo-loaded PDEδ and Arl3 to release lipidated cargo into cilia.

PubMed: 23559067
DOI: 10.1038/embor.2013.37

Experimental method

X-RAY DIFFRACTION (1.9 Å)