Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1

Jiqing Du, Marie-Kristin von Wrisberg, Burak Gulen, Matthias Stahl, Christian Pett, Christian Hedberg, Kathrin Lang (), Sabine Schneider () and Aymelt Itzen ()
Additional contact information
Jiqing Du: Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich
Marie-Kristin von Wrisberg: Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich, Institute for Advanced Study
Burak Gulen: Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich
Matthias Stahl: Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich
Christian Pett: Chemical Biology Center (KBC), Department of Chemistry, Umeå University
Christian Hedberg: Chemical Biology Center (KBC), Department of Chemistry, Umeå University
Kathrin Lang: Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich, Institute for Advanced Study
Sabine Schneider: Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Ludwig-Maximilians-University Munich
Aymelt Itzen: Center for Integrated Protein Science Munich (CIPSM), Department of Chemistry, Technical University of Munich

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Legionella pneumophila infects eukaryotic cells by forming a replicative organelle – the Legionella containing vacuole. During this process, the bacterial protein DrrA/SidM is secreted and manipulates the activity and post-translational modification (PTM) states of the vesicular trafficking regulator Rab1. As a result, Rab1 is modified with an adenosine monophosphate (AMP), and this process is referred to as AMPylation. Here, we use a chemical approach to stabilise low-affinity Rab:DrrA complexes in a site-specific manner to gain insight into the molecular basis of the interaction between the Rab protein and the AMPylation domain of DrrA. The crystal structure of the Rab:DrrA complex reveals a previously unknown non-conventional Rab-binding site (NC-RBS). Biochemical characterisation demonstrates allosteric stimulation of the AMPylation activity of DrrA via Rab binding to the NC-RBS. We speculate that allosteric control of DrrA could in principle prevent random and potentially cytotoxic AMPylation in the host, thereby perhaps ensuring efficient infection by Legionella.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-020-20702-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-020-20702-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-020-20702-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().