6sku | pdb_00006sku

Legionella effector AnkX in complex with human Rab1b

spinqualitylabelsall models 6sku, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6sku is a 2 chain structure with sequence from Homo sapiens and Legionella pneumophila subsp. pneumophila str. Philadelphia 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.2Å Ligands: GDP, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ANKX_LEGPH Virulence effector that plays a role in hijacking the host vesicular trafficking by recruiting the small guanosine triphosphatase (GTPase) Rab1 to the cytosolic face of the Legionella-containing vacuole (LCVs). Acts as a phosphocholine transferase by mediating the addition of phosphocholine to Ser residues of host RAB1 (RAB1A, RAB1B or RAB1C) and RAB35, leading to displacement of GDP dissociation inhibitors (GDI). Phosphocholination of target proteins also impairs accessibility to GTPase effector LepB. Can act on both GDP-bound and GTP-bound Rab proteins. Publication Abstract from PubMed The causative agent of Legionnaires disease, Legionella pneumophila, 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 beta 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. Legionella effector AnkX displaces the switch II region for Rab1b phosphocholination.,Ernst S, Ecker F, Kaspers MS, Ochtrop P, Hedberg C, Groll M, Itzen A Sci Adv. 2020 May 15;6(20):eaaz8041. doi: 10.1126/sciadv.aaz8041. eCollection, 2020 May. PMID:32440549 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also GTP-binding protein 3D structures Ras-related protein Rab 3D structures

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