4iik | pdb_00004iik

Legionella pneumophila effector

spinqualitylabelsall models 4iik, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4iik is a 1 chain structure with sequence from Legionella pneumophila subsp. pneumophila str. Philadelphia 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, GOL, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function SIDD_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 an adenosine monophosphate-protein hydrolase (de-AMPylase) by mediating the hydrolysis of adenosine 5'-monophosphate (AMP) to 'Tyr-77' of host RAB1B, thereby releasing RAB1B from bacterial phagosomes and rendering RAB1B accessible for inactivation by LepB. De-AMPylation of RAB1B cannot take place when LidA is bound to RAB1B. Publication Abstract from PubMed The covalent attachment of adenosine monophosphate (AMP) to proteins, a process called AMPylation (adenylylation), has recently emerged as a novel theme in microbial pathogenesis. Although several AMPylating enzymes have been characterized, the only known virulence protein with de-AMPylation activity is SidD from the human pathogen Legionella pneumophila. SidD de-AMPylates mammalian Rab1, a small GTPase involved in secretory vesicle transport, thereby targeting the host protein for inactivation. The molecular mechanisms underlying Rab1 recognition and de-AMPylation by SidD are unclear. Here, we report the crystal structure of the catalytic region of SidD at 1.6 A resolution. The structure reveals a phosphatase-like fold with additional structural elements not present in generic PP2C-type phosphatases. The catalytic pocket contains a binuclear metal-binding site characteristic of hydrolytic metalloenzymes, with strong dependency on magnesium ions. Subsequent docking and molecular dynamics simulations between SidD and Rab1 revealed the interface contacts and the energetic contribution of key residues to the interaction. In conjunction with an extensive structure-based mutational analysis, we provide in vivo and in vitro evidence for a remarkable adaptation of SidD to its host cell target Rab1 which explains how this effector confers specificity to the reaction it catalyses. Structural Basis for Rab1 De-AMPylation by the Legionella pneumophila Effector SidD.,Chen Y, Tascon I, Neunuebel MR, Pallara C, Brady J, Kinch LN, Fernandez-Recio J, Rojas AL, Machner MP, Hierro A PLoS Pathog. 2013 May;9(5):e1003382. doi: 10.1371/journal.ppat.1003382. Epub 2013, May 16. PMID:23696742 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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