title: Structural insights into the mechanism of GTPase activation in the GIMAP family.
abstract: GTPases of immunity-associated proteins (GIMAPs) are regulators of lymphocyte survival and homeostasis. We previously determined the structural basis of GTP-dependent GIMAP2 scaffold formation on lipid droplets. To understand how its GTP hydrolysis is activated, we screened for other GIMAPs on lipid droplets and identified GIMAP7. In contrast to GIMAP2, GIMAP7 displayed dimerization-stimulated GTP hydrolysis. The crystal structure of GTP-bound GIMAP7 showed a homodimer that assembled via the G domains, with the helical extensions protruding in opposite directions. We identified a catalytic arginine that is supplied to the opposing monomer to stimulate GTP hydrolysis. GIMAP7 also stimulated GTP hydrolysis by GIMAP2 via an analogous mechanism. Finally, we found GIMAP2 and GIMAP7 expression differentially regulated in several human T cell lymphoma lines. Our findings suggest that GTPase activity in the GIMAP family is controlled by homo- and heterodimerization. This may have implications for the differential roles of some GIMAPs in lymphocyte survival.
authors: Max-Delbrück-Centrum für Molekulare Medizin, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. david.schwefel@nimr.mrc.ac.uk
authors: David
authors: D
authors: Schwefel
authors: B Sivanandam
authors: BS
authors: Arasu
authors: Stephen F
authors: SF
authors: Marino
authors: Björn
authors: B
authors: Lamprecht
authors: Karl
authors: K
authors: Köchert
authors: Eva
authors: E
authors: Rosenbaum
authors: Jenny
authors: J
authors: Eichhorst
authors: Burkhard
authors: B
authors: Wiesner
authors: Joachim
authors: J
authors: Behlke
authors: Oliver
authors: O
authors: Rocks
authors: Stephan
authors: S
authors: Mathas
authors: Oliver
authors: O
authors: Daumke
mesh_terms: D002151:Calorimetry; D002460:Cell Line; D003460:Crystallization; D019281:Dimerization; D004789:Enzyme Activation / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D050356:Lipid Metabolism / Q000502:physiology; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D011487:Protein Conformation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000378:metabolism*; D014461:Ultracentrifugation
chemical_list: C520502:GIMAP7 protein, human; D008565:Membrane Proteins; C553225:GIMAP2 protein, human; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins