6sku
From Proteopedia
Legionella effector AnkX in complex with human Rab1b
Structural highlights
FunctionANKX_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.[1] [2] [3] [4] [5] Publication Abstract from PubMedThe 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[6] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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