The team, led by Aaron Lucius, professor of Chemistry, discovered that the E. coli protein ClpB (caseinolytic protease B) uses a novel mechanism to untangle protein aggregates. ClpB is an ATPase and belongs to the hexameric AAA+ superfamily of enzymes. It is produced when cells experience stressful conditions, such as high heat, that denature and aggregate proteins. The ClpB enzyme consists of six subunits that form a hexagon with a channel in the middle.
ClpB was long thought to function like its counterpart ClpA. ClpA feeds misfolded proteins through its central channel into the protease ClpP, where they are degraded. ClpA does this by a mechanism of “processive pulling”, continually feeding long strands of protein into ClpP. What Lucius and his team found, however, was surprising. "Oour results support a molecular mechanism where ClpB catalyzes protein disaggregation by tugging and releasing exposed tails or loops”, says Lucius.
They reason that such a “tugging” mechanism could be used by other enzymes, and may inform therapeutics for Alzheimer’s or Parkinson’s disease. According to Lucius, “we don’t know how proteins get tangled, but if we can study how proteins get disaggregated, it may have clinical relevance”.
Sources: Phys.org, Biochemical Journal, Wikipedia