Arginine-repressor protein from E. coli: A computational study

L. Lüley,¹ T. Stockner² and R. Ettrich¹

¹Laboratory of High Performance Computing, Institute of Physical Biology USB and Institute of Landscape Ecology AS CR, University of South Bohemia, Zámek 136, 373 33 Nové Hrady, Czech Republic, e-mail: luley@greentech.cz

²Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

Arginine biosynthesis in Escherichia coli is regulated by the negative feedback mechanism at the hand of the hexameric arginine repressor protein (ArgR) with the corepressor L-arginine.

ArgR differs from most other bacterial repressors in functioning as a hexamer. L-Arginine binds to ArgR in the C-terminal domain of the repressor. Binding to operator DNA occurs in the N-terminal domain. The molecular structures of both domains have recently been solved [1, 2], but due to the size of the ArgR and flexible linker region between C and N-terminal domains, the whole structure is still challenge for experimentalists.

Allosteric activation of the hexameric ArgR for specific operator DNA binding appears to involve alteration in its quaternary structure. Current models for activation include subunit assembly and/or domain rearrangements in response to binding of the coeffector L-arginine. It is supposed [3] that subunit assembly plays no role in activation, although communication among subunits of the ArgR hexamer is required for specific DNA binding. It is expected [3] that DNA is also an allosteric effector of ArgR.

We have built several ArgR homology models for Escherichia coli which were further refined by molecular dynamics. Currently the effect of binding of L-arginine on the quaternary structure of the repressor protein is examined using long molecular dynamics runs. Our results indicate a potential binding site for DNA on the N-domain of he activated repressor.

This research was supported by FRVS (3303/2005), by the Ministry of Education, Youth and Sports of the Czech Republic (MSM6007665808) and by the Academy of Sciences of the Czech Republic (Institutional research concept AVOZ60870520)

[1] Van Duyne, G. D., Ghosh, S., Maas, W. K. & Sigler, P. B. (1996). Structure of the oligomerization and L-arginine binding domain of the arginine repressor of Escherichia coli. J. Mol. Biol. 256, 377-391

[2] Grandori R., Lavoie T.A., Pflumm, M., Tian, G., Niersbach, H., Maas, W.K., Fairman, R. and Carey, J. (1995) ''The DNA-binding domain of the hexameric arginine repressor.'' J. Mol. Biol. 254, 150-162.

[3] Szwajkajzer, Danuta, Dai, Lizhong, Fukayama, June W., Abramczyk, Bozena, Fairman, Robert, and Carey, Jannette. 2001. Quantitative analysis of DNA binding by the E. coli arginine repressor. J. Mol. Biol. 312:949.