EspM2 is a RhoA guanine nucleotide exchange factor

Summary We investigated how the type III secretion system WxxxE effectors EspM2 of enterohaemorrhagic Escherichia coli, which triggers stress fibre formation, and SifA of Salmonella enterica serovar Typhimurium, which is involved in intracellular survival, modulate Rho GTPases. We identified a direc...

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Main Authors: Lillington, J, Bulgin, R, Berger, C, Lea, S, Matthews, S, Frankel, G, Garnett, J, Arbeloa, A
Format: Journal article
Language:English
Published: Wiley 2010
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author Lillington, J
Bulgin, R
Berger, C
Lea, S
Matthews, S
Frankel, G
Garnett, J
Arbeloa, A
author_facet Lillington, J
Bulgin, R
Berger, C
Lea, S
Matthews, S
Frankel, G
Garnett, J
Arbeloa, A
author_sort Lillington, J
collection OXFORD
description Summary We investigated how the type III secretion system WxxxE effectors EspM2 of enterohaemorrhagic Escherichia coli, which triggers stress fibre formation, and SifA of Salmonella enterica serovar Typhimurium, which is involved in intracellular survival, modulate Rho GTPases. We identified a direct interaction between EspM2 or SifA and nucleotide-free RhoA. Nuclear Magnetic Resonance Spectroscopy revealed that EspM2 has a similar fold to SifA and the guanine nucleotide exchange factor (GEF) effector SopE. EspM2 induced nucleotide exchange in RhoA but not in Rac1 or H-Ras, while SifA induced nucleotide exchange in none of them. Mutating W70 of the WxxxE motif or L118 and I127 residues, which surround the catalytic loop, affected the stability of EspM2. Substitution of Q124, located within the catalytic loop of EspM2, with alanine, greatly attenuated the RhoA GEF activity in vitro and the ability of EspM2 to induce stress fibres upon ectopic expression. These results suggest that binding of SifA to RhoA does not trigger nucleotide exchange while EspM2 is a unique Rho GTPase GEF.
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spelling oxford-uuid:1a04abc8-d560-4cfa-aa87-f2fe4f11e55c2022-03-26T10:52:20ZEspM2 is a RhoA guanine nucleotide exchange factorJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1a04abc8-d560-4cfa-aa87-f2fe4f11e55cEnglishSymplectic Elements at OxfordWiley2010Lillington, JBulgin, RBerger, CLea, SMatthews, SFrankel, GGarnett, JArbeloa, ASummary We investigated how the type III secretion system WxxxE effectors EspM2 of enterohaemorrhagic Escherichia coli, which triggers stress fibre formation, and SifA of Salmonella enterica serovar Typhimurium, which is involved in intracellular survival, modulate Rho GTPases. We identified a direct interaction between EspM2 or SifA and nucleotide-free RhoA. Nuclear Magnetic Resonance Spectroscopy revealed that EspM2 has a similar fold to SifA and the guanine nucleotide exchange factor (GEF) effector SopE. EspM2 induced nucleotide exchange in RhoA but not in Rac1 or H-Ras, while SifA induced nucleotide exchange in none of them. Mutating W70 of the WxxxE motif or L118 and I127 residues, which surround the catalytic loop, affected the stability of EspM2. Substitution of Q124, located within the catalytic loop of EspM2, with alanine, greatly attenuated the RhoA GEF activity in vitro and the ability of EspM2 to induce stress fibres upon ectopic expression. These results suggest that binding of SifA to RhoA does not trigger nucleotide exchange while EspM2 is a unique Rho GTPase GEF.
spellingShingle Lillington, J
Bulgin, R
Berger, C
Lea, S
Matthews, S
Frankel, G
Garnett, J
Arbeloa, A
EspM2 is a RhoA guanine nucleotide exchange factor
title EspM2 is a RhoA guanine nucleotide exchange factor
title_full EspM2 is a RhoA guanine nucleotide exchange factor
title_fullStr EspM2 is a RhoA guanine nucleotide exchange factor
title_full_unstemmed EspM2 is a RhoA guanine nucleotide exchange factor
title_short EspM2 is a RhoA guanine nucleotide exchange factor
title_sort espm2 is a rhoa guanine nucleotide exchange factor
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