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TitleUnique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1.
Journal, issue, pagesStructure, Vol. 31, Issue 3, Page 309-317.e5, Year 2023
Publish dateMar 2, 2023
AuthorsDhiraj Srivastava / Ravi P Yadav / Sneha Singh / Kimberly Boyd / Nikolai O Artemyev /
PubMed AbstractPhotoreceptor phosphodiesterase PDE6 is central for visual signal transduction. Maturation of PDE6 depends on a specialized chaperone complex of HSP90 with aryl hydrocarbon receptor-interacting ...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.
External linksStructure / PubMed:36657440 / PubMed Central
MethodsEM (single particle)
Resolution3.1 - 3.9 Å
Structure data

28332

8eoa

EMDB-28332: Cryo-EM structure of human HSP90B in the closed state
PDB-8eoa: Cryo-EM structure of human HSP90B-AIPL1 complex
Method: EM (single particle) / Resolution: 3.9 Å

28333

8eob

EMDB-28333, PDB-8eob:
Cryo-EM structure of human HSP90B in the closed state
Method: EM (single particle) / Resolution: 3.1 Å

Chemicals

ChemComp-ANP:
PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER / AMP-PNP, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
KeywordsCHAPERONE / HSP90B / AIPL1 / phosphodiesterase 6

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