Proteolysis of Rab32 by Salmonella GtgE induces an inactive GTPase conformation

Savitskiy, Sergey; Wachtel, Rudolf; Pourjafar-Dehkordi, Danial; Kang, Hyun-Seo; Trauschke, Vanessa; Lamb, Don C.; Sattler, Michael; Zacharias, Martin; Itzen, Aymelt

doi:10.1016/j.isci.2020.101940

Cited by 12 publications

(10 citation statements)

References 66 publications

(74 reference statements)

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“…Further, in order for Salmonella to manipulate the host endocytic pathway, several ras-associated binding (RAB) proteins have been reported to be directly targeted by effectors (e.g., GtgE, SopD and SopD2 (58)(59)(60). Based on our IPA analysis, autophagy has a positive activation z-score at 8 hpi (Figure 6A) with a predicted contribution of the RAB1A, RAB7A and RAB9A found to at higher abundancies at this time point in our DIA data.…”

Section: Discussionmentioning

confidence: 99%

Shift in vacuolar to cytosolic regime of infectingSalmonellafrom a dual proteome perspective

Fels

Willems

Meyer

et al. 2023

Preprint

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By applying dual proteome profiling to Salmonella enterica serovar Typhimurium (S. Typhimurium) encounters with its epithelial host (here, S. Typhimurium infected human HeLa cells), a detailed interdependent and holistic proteomic perspective on host-pathogen interactions over a time course of infection was obtained. Data-independent acquisition (DIA)-based proteomics was found to outperform data-dependent acquisition (DDA) workflows, especially in identifying the downregulated bacterial proteome response during infection progression infection by permitting quantification of low abundant bacterial proteins at early times of infection at low bacterial infection load. S. Typhimurium invasion and replication specific proteomic signatures in epithelial cells revealed interdependent host/pathogen specific responses besides pointing to putative novel infection markers and signalling responses.

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Section: Discussionmentioning

confidence: 99%

Shift in vacuolar to cytosolic regime of infectingSalmonellafrom a dual proteome perspective

Fels

Willems

Meyer

et al. 2023

Preprint

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“…GtgE has a high affinity for the GDP‐bound state of Rab32 and cleaves this GTPase within its regulatory switch I region (Wachtel et al, 2018). Proteolysis by GtgE induces an inactive GTPase conformation, stabilizing its interaction with its GDI and thus disturbs the downstream signaling of Rab32 (Savitskiy et al, 2021). SopD2 mimics the activity of eukaryotic GAPs and prefers to bind to a GTP‐bound form of Rab32.…”

Section: Inactivation Of Rab1 and Rab32 To Counteract Host Defensesmentioning

confidence: 99%

Determination of the Salmonella intracellular lifestyle by the diversified interaction of Type III secretion system effectors and host GTPases

Meng

Zhu

Shi

et al. 2022

WIREs Mechanisms of Disease

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Intracellular bacteria have developed sophisticated strategies to subvert the host endomembrane system to establish a stable replication niche. Small GTPases are critical players in regulating each step of membrane trafficking events, such as vesicle biogenesis, cargo transport, tethering, and fusion events.Salmonella is a widely studied facultative intracellular bacteria. Salmonella delivers several virulence proteins, termed effectors, to regulate GTPase dynamics and subvert host trafficking for their benefit. In this review, we summarize an updated and systematic understanding of the interactions between bacterial effectors and host GTPases in determining the intracellular lifestyle of Salmonella.

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“…GtgE cleaves Rab32 in the switch I region, between Gly59 and Val60 [172]. While the cleaved Rab32 remains folded, its GTP binding is significantly affected and the nucleotide no longer stabilizes Rab32 [173]. The structure of the GtgE-Rab32-GDP complex showed how GtgE recognizes Rab32 and delineated the catalytic mechanism.…”

Section: Inactivation Of G-proteins By Proteolysismentioning

confidence: 99%