8jo3

Cryo-EM structure of a Legionella effector complexed with actin and AMP

spinqualitylabelsall models 8jo3, resolution 2.66Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8jo3 is a 2 chain structure with sequence from Legionella sainthelensi and Oryctolagus cuniculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.66Å Ligands: AMP, ATP, CA Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A2H5FI52_9GAMM Publication Abstract from PubMed AMPylation is a post-translational modification in which AMP is added to the amino acid side chains of proteins(1,2). Here we show that, with ATP as the ligand and actin as the host activator, the effector protein LnaB of Legionella pneumophila exhibits AMPylase activity towards the phosphoryl group of phosphoribose on PR(R42)-Ub that is generated by the SidE family of effectors, and deubiquitinases DupA and DupB in an E1- and E2-independent ubiquitination process(3-7). The product of LnaB is further hydrolysed by an ADP-ribosylhydrolase, MavL, to Ub, thereby preventing the accumulation of PR(R42)-Ub and ADPR(R42)-Ub and protecting canonical ubiquitination in host cells. LnaB represents a large family of AMPylases that adopt a common structural fold, distinct from those of the previously known AMPylases, and LnaB homologues are found in more than 20 species of bacterial pathogens. Moreover, LnaB also exhibits robust phosphoryl AMPylase activity towards phosphorylated residues and produces unique ADPylation modifications in proteins. During infection, LnaB AMPylates the conserved phosphorylated tyrosine residues in the activation loop of the Src family of kinases(8,9), which dampens downstream phosphorylation signalling in the host. Structural studies reveal the actin-dependent activation and catalytic mechanisms of the LnaB family of AMPylases. This study identifies, to our knowledge, an unprecedented molecular regulation mechanism in bacterial pathogenesis and protein phosphorylation. Legionella effector LnaB is a phosphoryl AMPylase that impairs phosphosignalling.,Wang T, Song X, Tan J, Xian W, Zhou X, Yu M, Wang X, Xu Y, Wu T, Yuan K, Ran Y, Yang B, Fan G, Liu X, Zhou Y, Zhu Y Nature. 2024 May 22. doi: 10.1038/s41586-024-07573-z. PMID:38776962 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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