Presenter: Clarissa Weaver
Discussion summary:
We discussed an intriguing paper published in the January 16 issue of Cell, “Potentiated Hsp104 Variants Antagonize Diverse Proteotoxic Misfolding Events” (Jackrel et al., Cell 156, 170-182, 2014). Shorter and colleagues discovered mutations in the middle coiled-coil domain of Hsp104 that yielded enhanced activity of this chaperone protein, which acts to disaggregate toxic protein aggregates. Importantly, the mutant proteins with enhanced activity also promoted the proper localization of proteins, not only their disaggregation, and could remove amyloid structures that were already formed, in contrast to wildtype Hsp104.
Points that were discussed:
Discussion summary:
We discussed an intriguing paper published in the January 16 issue of Cell, “Potentiated Hsp104 Variants Antagonize Diverse Proteotoxic Misfolding Events” (Jackrel et al., Cell 156, 170-182, 2014). Shorter and colleagues discovered mutations in the middle coiled-coil domain of Hsp104 that yielded enhanced activity of this chaperone protein, which acts to disaggregate toxic protein aggregates. Importantly, the mutant proteins with enhanced activity also promoted the proper localization of proteins, not only their disaggregation, and could remove amyloid structures that were already formed, in contrast to wildtype Hsp104.
Points that were discussed:
- Are the new mutants hexameric? How could this be shown? (e.g. biophysical techniques)
- It would be interesting to take advantage of these proteins for solubilizing recalcitrant proteins during purification.
- Hypotheses for how these mutations cause the observed effects? Kinetic, structural changes - both?
- It is interesting to note that Hsp104 has different effects on different types of protein aggregates - e.g. yeast proteins vs. human proteins, prions.
