Structural Insights into the Mechanism of GTPase Activation in the GIMAP Family
2013; Elsevier BV; Volume: 21; Issue: 4 Linguagem: Inglês
10.1016/j.str.2013.01.014
ISSN1878-4186
AutoresDavid Schwefel, B. Sivanandam Arasu, Stephen F. Marino, Björn Lamprecht, Karl Köchert, Eva Rosenbaum, Jenny Eichhorst, Burkhard Wiesner, Joachim Behlke, Oliver Rocks, Stephan Mathas, Oliver Daumke,
Tópico(s)Genetics and Neurodevelopmental Disorders
ResumoSummaryGTPases 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.Highlights•GIMAP7 and GIMAP2 colocalize at lipid droplets in a human T-cell line•Structure of the GIMAP7 dimer reveals a catalytic arginine supplied in trans•GIMAP7 activates GTP hydrolysis of GIMAP2•Differential expression of GIMAPs in human anaplastic large cell lymphoma cell lines
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