Universität zu Köln

Schulte, Kathrin, Pawlowski, Nikolaus, Faelber, Katja, Froehlich, Chris, Howard, Jonathan ORCID: 0000-0003-2756-5143 and Daumke, Oliver (2016). The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion. BMC Biol., 14. LONDON: BMC. ISSN 1741-7007

Full text not available from this repository.

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schulte, Kathrin UNSPECIFIED UNSPECIFIED UNSPECIFIED Pawlowski, Nikolaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Faelber, Katja UNSPECIFIED UNSPECIFIED UNSPECIFIED Froehlich, Chris UNSPECIFIED UNSPECIFIED UNSPECIFIED Howard, Jonathan UNSPECIFIED orcid.org/0000-0003-2756-5143 UNSPECIFIED Daumke, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-281786
DOI:	10.1186/s12915-016-0236-7
Journal or Publication Title:	BMC Biol.
Volume:	14
Date:	2016
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1741-7007
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RESISTANCE GTPASES; TOXOPLASMA-GONDII; ENDOPLASMIC-RETICULUM; DOMAIN DIMERIZATION; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; MICE DEFICIENT; P47 GTPASES; INTERFERON; LRG-47 Multiple languages Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28178