Building a structural and functional model of the complex between the small lipidated GTPase Arf1 and its ArfGAP, ASAP1.

Most cell membrane signaling and trafficking are regulated by assembling dynamic signaling platforms associated with cell membrane surfaces in lipid and time-dependent fashion. This project focuses on mapping the interaction between ASAP1, a multidomain ArfGAP protein that correlates with poor prognosis in several cancers, with its substrate Arf1. We will use neutron reflectometry and model membranes. We recently combined NMR, NR, and MD to elucidate the membrane docking geometry and the fundamental interactions of the ASAP1 PH domain in the absence of Arf1 (O. Soubias et al. Sci. Adv. 30(6), 2020). We further characterized Arf1 on its own (manuscript in preparation). This work is a continuation of this project towards resolving the structure of the Arf1/PH complex at the membrane.