Conformational dynamics of the ClpB AAA+ protein disaggregase: molecular dynamics studies

Severe heat shock, cellular stress and mutations cause massive protein misfolding and aggregation resulting in loss of essential cellular activity. Molecular chaperones and ATP-dependent proteases maintain protein homeostasis by preventing the accumulation of misfolded proteins through refolding, disaggregation, or degradation. AAA+ (ATPases Associated with diverse cellular Activities) motor proteins assist protein disaggregation and degradation by mechanically pulling substrate proteins using a set of conserved pore loops protruding into the narrow central channel.