Javier Oroz and Douglas Laurents, from the "Manuel Rico" NMR laboratory, have characterized structural transitions in Orb2, a functional prion which is key for memory consolidation in Drosophila.

Recently, Science published the structural characterization of the mature amyloid fibrils formed by the Orb2 functional prion in Drosophila brain, which enabled to establish the structural basis for the process of memory consolidation in flies. However, we still do not understand in detail the structural transitions coupled to the fibril assembly process as the mechanism for memory consolidation mediated by Orb2. Orb2 contains a prion-like domain which forms the core of the amyloid fibrils. Using a novel assignment method, Oroz & Laurents, in collaboration with scientists from the Nova University of Lisboa, have characterized the structural and dynamic properties in solution of the prion-like domain of Orb2. Orb2 shows structural plasticity, and acquires alpha helical structure in a region of the protein particularly rich in Histidine residues at neutral pH, while at acidic pH Orb2 is fully disordered. Whereas Orb2 binds RNA at acidic pH, at neutral pH is unable to bind RNA or Ca+2, but binds Zn+2 and starts to oligomerize. Using the data obtained, the authors propose a model of the regulation of the functional amyloidogenesis of Orb2.

Javier Oroz, Sara S. Félix, Eurico J. Cabrita, Douglas V. Laurents. 

Structural transitions in Orb2 prion-like domain relevant for functional aggregation in memory consolidation. J. Biol. Chem. (2020) 295 (52): 18122-33.

doi: 10.1074/jbc.RA120.015211