Finally, an attempt was made to demonstrate an in vitro G-quadruplex unfolding activity of this helicase.
These results provide a framework for protein remodeling, wherein the physical attributes of a complex can limit the unfolding activity of its remodeler.
ATP-dependent proteases are able to unfold their target proteins, but this unfolding activity must be primed with a stretch of the substrate that is already disordered, resulting in multiple possibilities for selectivity and regulation.
Hyperactive ClpB-Y503D shows high ATPase and substrate unfolding activity even in the absence of Hsp70 (Oguchi et al., 2012; Seyffer et al., 2012).
Confirming its important regulatory role, deletion of motif 1 results in hyperactive ATPase and unfolding activity of ClpB-ΔM1 as well as cell toxicity, representing key characteristics of the hyperactive state (Oguchi et al., 2012).
The repressed mutant EClpB-E432A lacks the DnaK-dependent disaggregation activity, whereas the hyperactive EClpB-Y503D has higher ATPase and substrate unfolding activities even without Hsp70 partners but abolishes the disaggregation ability due to the loss of interaction with Hsp70 partners27.
In conclusion ClpB-ΔM1 exhibits the three major characteristics of hyperactive ClpB variants (high ATPase and unfolding activities linked to cellular toxicity), demonstrating the crucial regulatory role for motif 1 in interacting with an adjacent motif 2 to ensure tight activity control of ClpB.
Thermostability measurements revealed that the novel AldO is a highly thermostable enzyme with an unfolding temperature of 84 °C and an activity half-life at 75 °C of 112 min, prompting the name HotAldO.
Dzud is an unfolding disaster hence long-term support is needed for the recovery and future preparedness activities.
"We don't know what is going to happen next," said geologist James Dolan of USC, who has been watching the unfolding seismic activity.
