6px0 | pdb_00006px0

Crystal structure of the TPR domain of human aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1)

spinqualitylabelsall models 6px0, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6px0 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: BME, EDO, PEG, PG4 Gene: AIPL1, AIPL2 (HUMAN) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease [AIPL1_HUMAN] Leber congenital amaurosis;Cone rod dystrophy. The disease is caused by mutations affecting the gene represented in this entry. Function [AIPL1_HUMAN] May be important in protein trafficking and/or protein folding and stabilization. Publication Abstract from PubMed Phosphodiesterase-6 (PDE6) is key to both phototransduction and health of rods and cones. Proper folding of PDE6 relies on the chaperone activity of aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), and mutations in both PDE6 and AIPL1 can cause a severe form of blindness. Although AIPL1 and PDE6 are known to interact via the FK506-binding protein domain of AIPL1, the contribution of the tetratricopeptide repeat (TPR) domain of AIPL1 to its chaperone function is poorly understood. Here, we demonstrate that AIPL1-TPR interacts specifically with the regulatory Pgamma subunit of PDE6. Use of NMR chemical shift perturbation (CSP) mapping technique revealed the interface between the C-terminal portion of Pgamma and AIPL1-TPR. Our solution of the crystal structure of the AIPL1-TPR domain provided additional information, which together with the CSP data enabled us to generate a model of this interface. Biochemical analysis of chimeric AIPL1-AIP proteins supported this model and also revealed a correlation between the affinity of AIPL1-TPR for Pgamma and the ability of Pgamma to potentiate the chaperone activity of AIPL1. Based on these results, we present a model of the larger AIPL1-PDE6 complex. This supports the importance of simultaneous interactions of AIPL1-FK506-binding protein with the prenyl moieties of PDE6 and AIPL1-TPR with the Pgamma subunit during the folding and/or assembly of PDE6. This study sheds new light on the versatility of TPR domains in protein folding by describing a novel TPR-protein binding partner, Pgamma, and revealing that this subunit imparts AIPL1 selectivity for its client. Interaction of the tetratricopeptide repeat domain of aryl hydrocarbon receptor-interacting protein-like 1 with the regulatory Pgamma subunit of phosphodiesterase 6.,Yadav RP, Boyd K, Yu L, Artemyev NO J Biol Chem. 2019 Oct 25;294(43):15795-15807. doi: 10.1074/jbc.RA119.010666. Epub, 2019 Sep 5. PMID:31488544 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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