6YX5

Structure of DrrA from Legionella pneumophilia in complex with human Rab8a

Summary for 6YX5

• Entry DOI: 10.2210/pdb6yx5/pdb
• Descriptor: Ras-related protein Rab-8A, Multifunctional virulence effector protein DrrA, MAGNESIUM ION, ... (8 entities in total)
• Functional Keywords: vesicular trafficking virulence factor, cell invasion
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 60798.89

Authors

Schneider, S.,Du, J.,von Wrisberg, M.K.,Lang, K.,Itzen, A. (deposition date: 2020-04-30, release date: 2020-12-23, Last modification date: 2024-01-24)

Primary citation

Du, J.,Wrisberg, M.V.,Gulen, B.,Stahl, M.,Pett, C.,Hedberg, C.,Lang, K.,Schneider, S.,Itzen, A.
Rab1-AMPylation by Legionella DrrA is allosterically activated by Rab1.
Nat Commun, 12:460-460, 2021

PubMed 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.

PubMed: 33469029
DOI: 10.1038/s41467-020-20702-2

Experimental method

X-RAY DIFFRACTION (2.14 Å)