Structural insights into the mechanism of GTPase activation in the GIMAP family

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Item Type:	Article
Title:	Structural insights into the mechanism of GTPase activation in the GIMAP family
Creators Name:	Schwefel, D., Arasu, B.S., Marino, S.F., Lamprecht, B., Köchert, K., Rosenbaum, E., Eichhorst, J., Wiesner, B., Behlke, J., Rocks, O., Mathas, S. and Daumke, O.
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.
Keywords:	Calorimetry, Cell Line, Crystallization, Dimerization, Enzyme Activation, Fluorescence Microscopy, GTP Phosphohydrolases, GTP-Binding Proteins, Hydrolysis, Lipid Metabolism, Membrane Proteins, Molecular Models, Protein Conformation, Reverse Transcriptase Polymerase Chain Reaction, T-Lymphocytes, Ultracentrifugation
Source:	Structure
ISSN:	0969-2126
Publisher:	Cell Press
Volume:	21
Number:	4
Page Range:	550-559
Date:	2 April 2013
Official Publication:	https://doi.org/10.1016/j.str.2013.01.014
PubMed:	View item in PubMed

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