Release of monkeypox virus from within cells requires macropinocytosis. In addition to its role as a PI3K kinase, the E protein F13 of monkeypox virus also acts as a Dynamin GTPase. Dynamin GTPase activity is selectively regulated by the activity of PI3K. F13 helps facilitate this complicated invasion and membrane fusion by undergoing a series of conformational and membrane stability changes. The energy needed for conformational change and membrane destabilization comes from the hydrolysis of GTP bound to F13, and the energy released from GTP hydrolysis is much higher than that released from ATP hydrolysis. When F13's GTPase activity is stimulated by the PI3K domains, the PPM domain becomes exposed and can bind Mg2+. Its GTPase activity is stimulated when its G domain binds GTP with the aid of its GEF domain, and it is inactive when its GAP domain converts GTP to GDP. The GAP domain hydrolyzes GTP to GDP, and the GEF domain dissociates GDP from F13 so that F13 can bind to GTP. Hydrolysis of GTP provides the energy necessary for F13 to form lipid fusion, form fusion pores, and release viral RNA and related proteins, thus completing the fusion process. The PhoLip ATPase domain destabilizes viral and cellular membranes, allowing fusion pores to form.