Journal article
Interaction of the tetratricopeptide repeat domain of aryl hydrocarbon receptor-interacting protein-like 1 with the regulatory Pγ subunit of phosphodiesterase 6
The Journal of biological chemistry, Vol.294(43), pp.15795-15807
10/25/2019
DOI: 10.1074/jbc.RA119.010666
PMCID: PMC6816093
PMID: 31488544
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.
Details
- Title: Subtitle
- Interaction of the tetratricopeptide repeat domain of aryl hydrocarbon receptor-interacting protein-like 1 with the regulatory Pγ subunit of phosphodiesterase 6
- Creators
- Ravi P Yadav - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Kimberly Boyd - Department of Molecular Physiology and Biophysics, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Liping Yu - NMR Core Facility, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242Nikolai O Artemyev - Department of Ophthalmology and Visual Sciences, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.294(43), pp.15795-15807
- DOI
- 10.1074/jbc.RA119.010666
- PMID
- 31488544
- PMCID
- PMC6816093
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- United States
- Grant note
- P41 GM103622 / NIGMS NIH HHS R01 EY010843 / NEI NIH HHS S10 OD018090 / NIH HHS
- Language
- English
- Date published
- 10/25/2019
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Biochemistry and Molecular Biology; Medicine Administration; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070651702771
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