8EOB

Cryo-EM structure of human HSP90B in the closed state

Summary for 8EOB

• Entry DOI: 10.2210/pdb8eob/pdb
• EMDB information: 28333
• Descriptor: Heat shock protein HSP 90-beta, PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER, MAGNESIUM ION (3 entities in total)
• Functional Keywords: hsp90b, aipl1, phosphodiesterase 6, chaperone
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 175401.46

Authors

Srivastava, D.,Artemyev, N.O. (deposition date: 2022-10-02, release date: 2023-01-25, Last modification date: 2024-06-19)

Primary citation

Srivastava, D.,Yadav, R.P.,Singh, S.,Boyd, K.,Artemyev, N.O.
Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1.
Structure, 31:309-, 2023

PubMed 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.

PubMed: 36657440
DOI: 10.1016/j.str.2022.12.014

Experimental method

ELECTRON MICROSCOPY (3.1 Å)