6PX0
Crystal structure of the TPR domain of human aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1)
Summary for 6PX0
| Entry DOI | 10.2210/pdb6px0/pdb |
| Descriptor | Aryl-hydrocarbon-interacting protein-like 1, DI(HYDROXYETHYL)ETHER, TETRAETHYLENE GLYCOL, ... (6 entities in total) |
| Functional Keywords | aipl1 tpr, isomerase |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 19212.31 |
| Authors | Yadav, R.P.,Artemyev, N.O. (deposition date: 2019-07-24, release date: 2019-09-18, Last modification date: 2023-10-11) |
| Primary citation | Yadav, R.P.,Boyd, K.,Yu, L.,Artemyev, N.O. Interaction of the tetratricopeptide repeat domain of aryl hydrocarbon receptor-interacting protein-like 1 with the regulatory P gamma subunit of phosphodiesterase 6. J.Biol.Chem., 294:15795-15807, 2019 Cited by PubMed Abstract: 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 Pγ subunit of PDE6. Use of NMR chemical shift perturbation (CSP) mapping technique revealed the interface between the C-terminal portion of Pγ 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 Pγ and the ability of Pγ 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 Pγ 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, Pγ, and revealing that this subunit imparts AIPL1 selectivity for its client. PubMed: 31488544DOI: 10.1074/jbc.RA119.010666 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.55 Å) |
Structure validation
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