7L7I
Cryo-EM structure of Hsp90:FKBP51:p23 closed-state complex
Summary for 7L7I
| Entry DOI | 10.2210/pdb7l7i/pdb |
| Related | 7L7J |
| EMDB information | 23213 23214 |
| Descriptor | Peptidyl-prolyl cis-trans isomerase FKBP5, Heat shock protein HSP 90-alpha, Prostaglandin E synthase 3, ... (4 entities in total) |
| Functional Keywords | isomerase-chaperone complex, isomerase/chaperone |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 240586.43 |
| Authors | Lee, K.,Thwin, A.C.,Tse, E.,Gates, S.N.,Southworth, D.R. (deposition date: 2020-12-28, release date: 2021-08-25, Last modification date: 2024-05-29) |
| Primary citation | Lee, K.,Thwin, A.C.,Nadel, C.M.,Tse, E.,Gates, S.N.,Gestwicki, J.E.,Southworth, D.R. The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state. Mol.Cell, 81:3496-, 2021 Cited by PubMed Abstract: The Hsp90 chaperone promotes folding and activation of hundreds of client proteins in the cell through an ATP-dependent conformational cycle guided by distinct cochaperone regulators. The FKBP51 immunophilin binds Hsp90 with its tetratricopeptide repeat (TPR) domain and catalyzes peptidyl-prolyl isomerase (PPIase) activity during folding of kinases, nuclear receptors, and tau. Here we determined the cryoelectron microscopy (cryo-EM) structure of the human Hsp90:FKBP51:p23 complex to 3.3 Å, which, together with mutagenesis and crosslinking analyses, reveals the basis for cochaperone binding to Hsp90 during client maturation. A helix extension in the TPR functions as a key recognition element, interacting across the Hsp90 C-terminal dimer interface presented in the closed, ATP conformation. The PPIase domain is positioned along the middle domain, adjacent to Hsp90 client binding sites, whereas a single p23 makes stabilizing interactions with the N-terminal dimer. With this architecture, FKBP51 is positioned to act on specific client residues presented during Hsp90-catalyzed remodeling. PubMed: 34380015DOI: 10.1016/j.molcel.2021.07.023 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.3 Å) |
Structure validation
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