The structure of the apo-PIWI HSP90 complex

Authors

Donlon, P., Sotelo-Parrilla, P., MacKenzie MacLeod, D., Rosinska, A., Chowdhury, T., Leith, K. I., Zoch, A., Spanos, C., Cook, A. G., Jeyaprakash, A. A., OCarroll, D.

Abstract

PIWI proteins are members of the Argonaute family and together with piRNAs protect metazoan germlines from transposons. PIWI proteins adopt a bi-lobed architecture with a central RNA-binding channel. HSP90 function has been linked to piRNA biogenesis, but the precise molecular mechanism is unresolved. Using the mammalian embryonic piRNA pathway as a model system, we find compelling evidence for the existence of PIWIL2- (MILI-) and PIWIL4- (MIWI2-) HSP90 complexes in foetal testis. We purify apo-PIWIL4-HSP90 from cells and determine its structure by cryo-electron microscopy. Distinct from piRNA-bound PIWI, apo-PIWIL4 adopts a unique and open conformation. The HSP90 dimer binds and unfolds PIWIs linker 1 domain. PIWIL4s N domain and the RNA-binding PAZ-MID-PIWI module are placed on opposite sides of the HSP90 dimers lumen. We further demonstrate that PIWI-HSP90 complexes, the open apo-PIWI conformation, and the HSP90 lumen-binding peptide are conserved features of PIWI proteins.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 11 Jul 2026.

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