The BRICHOS domain is a molecular chaperone known for its ability to prevent amyloid and amorphous protein aggregation, playing a critical role in protecting cells from protein misfolding. ZoBio has an active collaboration with the Karolinska Institutet, where we are exploring the Bri2 BRICHOS protein and its potential as a therapeutic target for diseases related to protein misfolding, such as Alzheimer's. In a recent publication in Protein Science, our collaborators Gefei Chen and Janne Johansson investigated the molecular mechanisms by which the BRICHOS domain prevents both amyloid and amorphous protein aggregation, employing structural modeling, biochemical, and biophysical methods, including cryo-electron microscopy (cryo-EM). Single-particle cryo-EM provided structural models revealing how the hydrophobic regions of Bri2 BRICHOS become exposed and assemble during oligomerization, creating binding sites for amorphous protein aggregates. To further characterize higher-order assemblies of Bri2 BRICHOS, we used size-exclusion chromatography coupled to multi-angle light scattering (SEC-MALS). SEC-MALS confirmed the polydispersity of BRICHOS oligomers and allowed us to calculate the molar mass of the most representative species in solution, consistent with earlier biochemical data and cryo-EM observations.

In addition to structural and biophysical research on the Bri2 BRICHOS protein, our collaboration with Janne Johansson's group also focuses on developing small molecules that modulate BRICHOS activity, offering exciting therapeutic potential. We invite you to follow our ongoing journey as we continue to unlock the therapeutic possibilities of BRICHOS and its applications in neurodegenerative diseases!