Structural basis for DNA-mediated allosteric regulation facilitated by the AAA+ module of Lon protease
Journal
Acta Crystallographica Section D: Biological Crystallography
Journal Volume
70
Journal Volume
70
Journal Issue
2
Journal Issue
2
Pages
218-230
Start Page
218
End Page
230
ISSN
13990047
Date Issued
2014-02
Author(s)
Lee, Alan Yueh-Luen
Chen, Yu-Da
Chang, Yu-Yung
Lin, Yu-Ching
Chang, Chi-Fon
Huang, Shing-Jong
Wu, Shih-Hsiung
Abstract
Lon belongs to a unique group of AAA+ proteases that bind DNA. However, the DNA-mediated regulation of Lon remains elusive. Here, the crystal structure of the α subdomain of the Lon protease from Brevibacillus thermoruber (Bt-Lon) is presented, together with biochemical data, and the DNA-binding mode is delineated, showing that Arg518, Arg557 and Arg566 play a crucial role in DNA binding. Electrostatic interactions contributed by arginine residues in the AAA+ module are suggested to be important to DNA binding and allosteric regulation of enzymatic activities. Intriguingly, Arg557, which directly binds DNA in the α subdomain, has a dual role in the negative regulation of ATPase stimulation by DNA and in the domain-domain communication in allosteric regulation of Bt-Lon by substrate. In conclusion, structural and biochemical evidence is provided to show that electrostatic interaction in the AAA+ module is important for DNA binding by Lon and allosteric regulation of its enzymatic activities by DNA and substrate.
Subjects
AAA+ proteases
allosteric regulation
DNA binding
Lon proteases
Type
journal article