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The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion

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Item Type:Article
Title:The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion
Creators Name:Schulte, K. and Pawlowski, N. and Faelber, K. and Fröhlich, C. and Howard, J. and Daumke, O.
Abstract:BACKGROUND: The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization. RESULTS: We determined the crystal structure of an oligomerization-impaired Irga6 mutant bound to a non-hydrolyzable GTP analog. Contrary to the previous model, the structure shows that the GTPase domains dimerize in a parallel fashion. The nucleotides in the center of the interface participate in dimerization by forming symmetric contacts with each other and with the switch I region of the opposing Irga6 molecule. The latter contact appears to activate GTP hydrolysis by stabilizing the position of the catalytic glutamate 106 in switch I close to the active site. Further dimerization contacts involve switch II, the G4 helix and the trans stabilizing loop. CONCLUSIONS: The Irga6 structure features a parallel GTPase domain dimer, which appears to be a unifying feature of all dynamin and septin superfamily members. This study contributes important insights into the assembly and catalytic mechanisms of IRG proteins as prerequisite to understand their anti-microbial action.
Keywords:Innate Immunity, IRG Proteins, GTPase, Dynamin Superfamily, Dimerization, Oligomerization, Animals, Mice
Source:BMC Biology
ISSN:1741-7007
Publisher:BioMed Central (U.K.)
Volume:14
Number:1
Page Range:14
Date:2 March 2016
Official Publication:https://doi.org/10.1186/s12915-016-0236-7
PubMed:View item in PubMed

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