8YAC

Funes-induced Orb2 amyloid like endogenous Orb2 amyloid

Summary for 8YAC

• Entry DOI: 10.2210/pdb8yac/pdb
• EMDB information: 39095
• Descriptor: Translational regulator orb2 (1 entity in total)
• Functional Keywords: translator regulator, chaperone, protein fibril
• Biological source: Drosophila melanogaster (fruit fly)
• Total number of polymer chains: 9
• Total formula weight: 35767.53

Authors

Hervas, R.,Si, K. (deposition date: 2024-02-08, release date: 2025-09-03, Last modification date: 2026-03-18)

Primary citation

Patton, K.,Yi, Y.,Burt, R.,Ng, K.K.,Mukhi, M.,Khaki, P.S.S.,Hervas, R.,Si, K.
A J-domain protein enhances memory by promoting physiological amyloid formation in Drosophila.
Proc.Natl.Acad.Sci.USA, 123:e2516310123-e2516310123, 2026

PubMed Abstract: Memory requires experience-dependent alterations in the synaptic proteome. Chaperones interface between the environment and the proteome. Manipulating J-domain protein (JDP) chaperones, the most diverse family of chaperones, in a neuronal circuit that encodes associative long-term memories, we identified yet uncharacterized JDPs that transduce sensory cues. One of these JDPs, CG10375, which we named Funes, enhances memory when overexpressed and impairs memory when functionally impaired. Funes overexpression enhances memory formation even when sensory stimuli are suboptimal. At the circuit level, Funes acts on neurons where conditioned and unconditioned stimuli converge to form associative memories. From a proteomic-based screen, we found that overexpression of Funes changes the solubility of a small subset of proteins, one of which is the mRNA-binding protein Orb2. Combining in vitro and in vivo biophysical, biochemical, and cryo-EM structural analyses, we found that Funes associates with oligomeric Orb2 and promotes the formation of translationally active amyloids. Perturbation of the conserved J domain eliminates the ability of Funes to facilitate amyloid assembly and promote memory. We posit that the brain harbors chaperones that influence memory by regulating physiological amyloid formation.

PubMed: 41615743
DOI: 10.1073/pnas.2516310123

Experimental method

ELECTRON MICROSCOPY (3.1 Å)