Fig. 3: LONP1 in the substrate-bound conformation contains an inactive protease site.
From: Structures of the human LONP1 protease reveal regulatory steps involved in protease activation
a Surface representation of substrate-bound LONP1 showing a break in the protease domains between the highest subunit, ATP1, and its neighboring subunit, ATP2, highlighted using a dashed box. b The protease domains from ATP1 and ATP2 are shown using a ribbon representation, with the inactive active sites denoted by dashed boxes. c Close-up view of the proteolytic active site highlighting how the loop containing the catalytic serine (S855) is folded into a 310 helix and an aspartic acid (D842) prevents the formation of the serine (S855)-lysine (K898) catalytic dyad. The electron microscopy density for this region is shown as a gray mesh. d Superimposing the six protease domains of the substrate-bound H. sapiens LONP1 shows that all protease domains adopt an inactive conformation, despite having substrate bound within the ATPase channel. e A superimposition of all six protease domains in substrate-bound Y. pestis LON shows that all protease domains adopt an activated conformation where the 310 helix has unfolded to produce a binding groove to receive substrate, the aspartic acid (D676) is moved away from the active site, and the serine (S679)-lysine (722) catalytic dyad is positioned for peptide hydrolysis.
