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Du J, Wrisberg MV, Gulen B, Stahl M, Pett C, Hedberg C, Lang K, Schneider S, Itzen A
Nat Commun 12 (1) 460 [2021-01-19; online 2021-01-19]
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.
PubMed 33469029
DOI 10.1038/s41467-020-20702-2
Crossref 10.1038/s41467-020-20702-2
pmc: PMC7815794
pii: 10.1038/s41467-020-20702-2