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Savitskiy, S.* ; Wachtel, R.* ; Pourjafar-Dehkordi, D.* ; Kang, H.-S. ; Trauschke, V.* ; Lamb, D.C.* ; Sattler, M. ; Zacharias, M.* ; Itzen, A.*

Proteolysis of Rab32 by Salmonella GtgE induces an inactive GTPase conformation.

iScience 24:101940 (2021)
Verlagsversion Forschungsdaten DOI
Open Access Gold
Creative Commons Lizenzvertrag

Rab GTPases are central regulators of intracellular vesicular trafficking. They are frequently targeted by bacterial pathogens through post-translational modifications. Salmonella typhimurium secretes the cysteine protease GtgE during infection, leading to a regioselective proteolytic cleavage of the regulatory switch I loop in the small GTPases of the Rab32 subfamily. Here, using a combination of biochemical methods, molecular dynamics simulations, NMR spectroscopy, and single-pair Förster resonance energy transfer, we demonstrate that the cleavage of Rab32 causes a local increase of conformational flexibility in both switch regions. Cleaved Rab32 maintains its ability to interact with the GDP dissociation inhibitor (GDI). Interestingly, the Rab32 cleavage enables GDI binding also with an active GTP-bound Rab32 in vitro. Furthermore, the Rab32 proteolysis provokes disturbance in the interaction with its downstream effector VARP. Thus, the proteolysis of Rab32 is not a globally degradative mechanism but affects various biochemical and structural properties of the GTPase in a diverse manner.

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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Microbiology ; Molecular Structure; Structural Basis; Single-molecule; Signal-transduction; Defense Pathway; Protein; Effector; Trafficking; Complex; Dissociation; Binding
ISSN (print) / ISBN 2589-0042
e-ISSN 2589-0042
Zeitschrift iScience
Quellenangaben Band: 24, Heft: 1, Seiten: , Artikelnummer: 101940 Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam ; Bosten ; London ; New York ; Oxford ; Paris ; Philadelphia ; San Diego ; St. Louis
Begutachtungsstatus Peer reviewed
Förderungen German Research Foundation DFG