Please use this identifier to cite or link to this item:
https://hdl.handle.net/10356/100154
Title: | A P-loop mutation in Gα subunits prevents transition to the active state : implications for G-protein signaling in fungal pathogenesis | Authors: | Siderovski, David P. Bosch, Dustin E. Willard, Francis S. Kimple, Adam J. Willard, Melinda D. Naqvi, Naweed Issak. Ramanujam, Ravikrishna. |
Keywords: | DRNTU::Science::Biological sciences | Issue Date: | 2012 | Source: | Bosch, D. E., Willard, F. S., Ramanujam, R., Kimple, A. J., Willard, M. D., Naqvi, N. I., et al. (2012). A P-loop mutation in Gα subunits prevents transition to the active state: Implications for G-protein signaling in fungal pathogenesis. PLoS Pathogens, 8(2), e1002553. | Series/Report no.: | PLoS pathogens | Abstract: | Heterotrimeric G-proteins are molecular switches integral to a panoply of different physiological responses that many organisms make to environmental cues. The switch from inactive to active Gαβγ heterotrimer relies on nucleotide cycling by the Gα subunit: exchange of GTP for GDP activates Gα, whereas its intrinsic enzymatic activity catalyzes GTP hydrolysis to GDP and inorganic phosphate, thereby reverting Gα to its inactive state. In several genetic studies of filamentous fungi, such as the rice blast fungus Magnaporthe oryzae, a G42R mutation in the phosphate-binding loop of Gα subunits is assumed to be GTPase-deficient and thus constitutively active. Here, we demonstrate that Gα(G42R) mutants are not GTPase deficient, but rather incapable of achieving the activated conformation. Two crystal structure models suggest that Arg-42 prevents a typical switch region conformational change upon Gαi1(G42R) binding to GDP·AlF4− or GTP, but rotameric flexibility at this locus allows for unperturbed GTP hydrolysis. Gα(G42R) mutants do not engage the active state-selective peptide KB-1753 nor RGS domains with high affinity, but instead favor interaction with Gβγ and GoLoco motifs in any nucleotide state. The corresponding Gαq(G48R) mutant is not constitutively active in cells and responds poorly to aluminum tetrafluoride activation. Comparative analyses of M. oryzae strains harboring either G42R or GTPase-deficient Q/L mutations in the Gα subunits MagA or MagB illustrate functional differences in environmental cue processing and intracellular signaling outcomes between these two Gα mutants, thus demonstrating the in vivo functional divergence of G42R and activating G-protein mutants. | URI: | https://hdl.handle.net/10356/100154 http://hdl.handle.net/10220/10955 |
ISSN: | 1553-7366 | DOI: | 10.1371/journal.ppat.1002553 | Schools: | School of Biological Sciences | Rights: | © 2012 The Authors. This paper was published in PLoS Pathogens and is made available as an electronic reprint (preprint) with permission of The Authors. The paper can be found at the following official DOI: [http://dx.doi.org/10.1371/journal.ppat.1002553]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. | Fulltext Permission: | open | Fulltext Availability: | With Fulltext |
Appears in Collections: | SBS Journal Articles |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
40. A P-loop mutation in Gα subunits prevents transition to the active state.pdf | 2.87 MB | Adobe PDF | View/Open |
SCOPUSTM
Citations
20
27
Updated on Mar 17, 2024
Web of ScienceTM
Citations
10
25
Updated on Oct 25, 2023
Page view(s) 50
592
Updated on Mar 17, 2024
Download(s) 10
344
Updated on Mar 17, 2024
Google ScholarTM
Check
Altmetric
Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.