Fig. 8: Proposed mechanism of Arf regulation by ASAP1 PH domain.
From: An active allosteric mechanism in ASAP1-mediated Arf1 GTP hydrolysis redefines PH domain function
A Kinetic modeling: Fraction of GTP hydrolyzed in 3 min by either ZA or PZA. From right to left, solid curves are for ZA (blue), PZA without PI(4,5)P2 (orange), and PZA with PI(4,5)P2 (red). Points represent experimental data and lines are predictions from optimized kinetic ODE model. In all cases where PI(4,5)P2 is present its concentration is 5 mol%. B Relative contribution of membrane recruitment, binding and allostery to GAP activity by the ASAP1 PH domain. C Proposed mechanism of Arf regulation by ASAP1 PH domain. The PH domain binds PI(4,5)P2 on the membrane (recruitment), forms a complex with Arf (binding), and induces motion of switch 1 controlled by Lys391 (part of XVK motif, see Fig. 9), and the PH domain N terminal extension—that results in a reduction in charge density on the γ phosphate such that Arf bound to ASAP1 PH is primed for efficient GTP hydrolysis. Source data are provided as a Source data file.
