Interaction of the tetratricopeptide repeat domain of aryl hydrocarbon receptor-interacting protein-like 1 with the regulatory P? subunit of phosphodiesterase 6.

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 P? subunit of PDE6. Use of NMR chemical shift perturbation (CSP) mapping technique revealed the interface between the C-terminal portion of P? 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 P? and the ability of P? 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 P? 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, P?, and revealing that this subunit imparts AIPL1 selectivity for its client.

SUBMITTER: Yadav RP 

PROVIDER: S-EPMC6816093 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature