Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1

Dhiraj Srivastava; Ravi P Yadav; Sneha Singh; Kimberly Boyd; Nikolai O Artemyev

doi:10.1016/j.str.2022.12.014

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Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1

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Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1

Dhiraj Srivastava, Ravi P Yadav, Sneha Singh, Kimberly Boyd and Nikolai O Artemyev

Structure (London), Vol.31(3), pp.309-317.e5

03/2023

DOI: 10.1016/j.str.2022.12.014

PMCID: PMC9992320

PMID: 36657440

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Abstract

Photoreceptor phosphodiesterase PDE6 is central for visual signal transduction. Maturation of PDE6 depends on a specialized chaperone complex of HSP90 with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1). Disruption of PDE6 maturation underlies a severe form of retina degeneration. Here, we report a 3.9 Å cryoelectron microscopy (cryo-EM) structure of the complex of HSP90 with AIPL1. This structure reveals a unique interaction of the FK506-binding protein (FKBP)-like domain of AIPL1 with HSP90 at its dimer interface. Unusually, the N terminus AIPL1 inserts into the HSP90 lumen in a manner that was observed previously for HSP90 clients. Deletion of the 7 N-terminal residues of AIPL1 decreased its ability to cochaperone PDE6. Multi-body refinement of the cryo-EM data indicated large swing-like movements of AIPL1-FKBP. Modeling the complex of HSP90 with AIPL1 using crosslinking constraints indicated proximity of the mobile tetratricopeptide repeat (TPR) domain with the C-terminal domain of HSP90. Our study establishes a framework for future structural studies of PDE6 maturation.

Protein Folding

HSP90

chaperone

phosphodiesterase 6

photoreceptor

AIPL1

phototransduction

Details

Title: Subtitle: Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1
Creators: Dhiraj Srivastava - University of Iowa
Ravi P Yadav - University of Iowa
Sneha Singh - University of Iowa
Kimberly Boyd - University of Iowa
Nikolai O Artemyev
Resource Type: Journal article
Publication Details: Structure (London), Vol.31(3), pp.309-317.e5
DOI: 10.1016/j.str.2022.12.014
PMID: 36657440
PMCID: PMC9992320
ISSN: 0969-2126
eISSN: 1878-4186
Language: English
Electronic publication date: 01/16/2023
Date published: 03/2023
Academic Unit: Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
Record Identifier: 9984362359302771

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