Next Article in Journal
Knowledge Generation with Rule Induction in Cancer Omics
Previous Article in Journal
Association of Complement Factor D and H Polymorphisms with Recurrent Pregnancy Loss
Open AccessArticle

GTP Binding Is Necessary for the Activation of a Toxic Mutant Isoform of the Essential GTPase ObgE

1
Centre of Microbial and Plant Genetics, KU Leuven—University of Leuven, Kasteelpark Arenberg 20 Box 2460, B-3001 Leuven, Belgium
2
VIB-KU Leuven Center for Microbiology, Kasteelpark Arenberg 20 Box 2460, B-3001 Leuven, Belgium
3
Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium
4
VIB-VUB Center for Structural Biology, Pleinlaan 2, B-1050 Brussels, Belgium
5
Imec, Kapeldreef 75, B-3001 Leuven, Belgium
*
Author to whom correspondence should be addressed.
M.F. and J.M. are joint senior authors.
Int. J. Mol. Sci. 2020, 21(1), 16; https://doi.org/10.3390/ijms21010016
Received: 4 November 2019 / Revised: 11 December 2019 / Accepted: 17 December 2019 / Published: 18 December 2019
(This article belongs to the Section Molecular Microbiology)
Even though the Obg protein is essential for bacterial viability, the cellular functions of this universally conserved GTPase remain enigmatic. Moreover, the influence of GTP and GDP binding on the activity of this protein is largely unknown. Previously, we identified a mutant isoform of ObgE (the Obg protein of Escherichia coli) that triggers cell death. In this research we explore the biochemical requirements for the toxic effect of this mutant ObgE* isoform, using cell death as a readily accessible read-out for protein activity. Both the absence of the N-terminal domain and a decreased GTP binding affinity neutralize ObgE*-mediated toxicity. Moreover, a deletion in the region that connects the N-terminal domain to the G domain likewise abolishes toxicity. Taken together, these data indicate that GTP binding by ObgE* triggers a conformational change that is transmitted to the N-terminal domain to confer toxicity. We therefore conclude that ObgE*–GTP, but not ObgE*–GDP, is the active form of ObgE* that is detrimental to cell viability. Based on these data, we speculate that also for wild-type ObgE, GTP binding triggers conformational changes that affect the N-terminal domain and thereby control ObgE function. View Full-Text
Keywords: Obg; ObgE; GTPase; GTP binding; Escherichia coli Obg; ObgE; GTPase; GTP binding; Escherichia coli
Show Figures

Graphical abstract

MDPI and ACS Style

Dewachter, L.; Deckers, B.; Martin, E.; Herpels, P.; Gkekas, S.; Versées, W.; Verstraeten, N.; Fauvart, M.; Michiels, J. GTP Binding Is Necessary for the Activation of a Toxic Mutant Isoform of the Essential GTPase ObgE. Int. J. Mol. Sci. 2020, 21, 16.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop