Fig. 5: Model for the mechanistic role of the NTD in Lon-mediated proteolysis in bacteria under various environmental conditions.
From: Structural basis for the allosteric activation of Lon by the heat shock protein LarA
a Cartoon illustrating six NTDs distributed around the tri-tyrosine substrate-entry pore (denoted by three Ys) of hexameric Lon, drawn in top view. Each NTD harbors a binding pocket for the C-terminal aromatic or hydrophobic residues of the protein or peptide substrates. b An NTD can bind to a folded substrate, which is often overexpressed in cells under stress conditions, and induce a deformation to expose its hydrophobic core to mediate hydrophobic interactions with other substrate molecules of the same or different species, which leads to local or partially unfolding of protein substrates to facilitate binding of their C-terminal degrons to the triple tyrosine residues in the entry pore. Similar substrate-mediated hydrophobic interactions may occur by docking to the NTDs of unfolded protein substrates, which are accumulated in cells during protein unfolding stress (c) or degron peptides introduced to activate Lon-mediated proteolysis in vitro (d).
