TITLE:
Inhibition of Lon protease by bacterial lipopolisaccharide (LPS) though inhibition of ATPase
AUTHORS:
Nahoko Sugiyama, Noriko Minami, Yoshiyuki Ishii, Fumio Amano
KEYWORDS:
ATPase; Lipid A; Lipopolysaccharide (LPS); Lon; Protease
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.4,
April
30,
2013
ABSTRACT: Lon protease, an ATP-dependent protease in Escherichia coli, degrades
abnormal proteins and regulates several important cellular functions. Here we
show novel inhibitory effects of lipopolysaccharide (LPS) on Lon protease
activities. LPS inhibited the peptidase, protease, and ATPase activities of
Lon; and a dose-response study showed that LPS at low doses more effectively
inhibited the ATPase activity than the peptidase one, suggesting different
susceptibility to LPS of these activities associated with Lon. Structure-activity relationship studies revealed that
ReLPS, detoxified LPS, and mono-phosphoryl as well as diphosphoryl
lipid A, also showed similar inhibition, suggesting that neither O-antigen
polysaccharide nor O-acyl chain, but rather phosphate groups in the lipid A
domain, seem to have been responsible for the inhibitory effects. Besides,
LPS was co-precipitated with Lon by an anti-Lon antibody, showing the direct
binding of LPS to Lon. These results suggest that LPS bound to Lon and
inhibited the protease activity of Lon by inhibiting its ATPase activity. These
results also seem to be another example of a negatively charged phosphate
group in membrane components of Escherichia coli being involved in the
regulation of protease activity of Lon through binding to Lon and inhibiting
its ATPase activity, as in the case of cardiolipin.