5fph
The GTPase domains of the immunity-related Irga6 dimerize in a parallel head-to-head fashion
Structural highlights
FunctionIIGP1_MOUSE GTPase with low activity. Has higher affinity for GDP than for GTP. Plays a role in resistance to intracellular pathogens. Required for disruption of the parasitophorous vacuole formed following T.gondii infection and subsequent killing of the parasite. Mediates resistance to C.trachomatis infection by targeting bacterial inclusions to autophagosomes for subsequent lysosomal destruction.[1] [2] [3] [4] Publication Abstract from PubMedBACKGROUND: 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. The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion.,Schulte K, Pawlowski N, Faelber K, Frohlich C, Howard J, Daumke O BMC Biol. 2016 Mar 2;14:14. doi: 10.1186/s12915-016-0236-7. PMID:26934976[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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