Effector AnkX Displaces the Switch II Region for Rab1b Phosphocholination

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 May 23

PMID 32440549

Citations 8

Authors

Stefan Ernst

Felix Ecker

Marietta S Kaspers

Philipp Ochtrop

Christian Hedberg

Michael Groll

Aymelt Itzen

Affiliations

Soon will be listed here.

Abstract

The causative agent of Legionnaires disease, , translocates the phosphocholine transferase AnkX during infection and thereby posttranslationally modifies the small guanosine triphosphatase (GTPase) Rab1 with a phosphocholine moiety at S76 using cytidine diphosphate (CDP)-choline as a cosubstrate. The molecular basis for Rab1 binding and enzymatic modification have remained elusive because of lack of structural information of the low-affinity complex with AnkX. We combined thiol-reactive CDP-choline derivatives with recombinantly introduced cysteines in the AnkX active site to covalently capture the heterocomplex. The resulting crystal structure revealed that AnkX induces displacement of important regulatory elements of Rab1 by placing a β sheet into a conserved hydrophobic pocket, thereby permitting phosphocholine transfer to the active and inactive states of the GTPase. Together, the combination of chemical biology and structural analysis reveals the enzymatic mechanism of AnkX and the family of filamentation induced by cyclic adenosine monophosphate (FIC) proteins.

Citing Articles

Dephosphocholination by Legionella effector Lem3 functions through remodelling of the switch II region of Rab1b.

Kaspers M, Pogenberg V, Pett C, Ernst S, Ecker F, Ochtrop P Nat Commun. 2023; 14(1):2245.

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AMPylation of small GTPases by Fic enzymes.

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Diversity and function of arthropod endosymbiont toxins.

Massey J, Newton I Trends Microbiol. 2021; 30(2):185-198.

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Specificity of AMPylation of the human chaperone BiP is mediated by TPR motifs of FICD.

Fauser J, Gulen B, Pogenberg V, Pett C, Pourjafar-Dehkordi D, Krisp C Nat Commun. 2021; 12(1):2426.

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