“…In addition to serving as a membrane anchor, this helix has been demonstrated to serve a critical role in membrane remodeling events including induction of membrane curvature and driving membrane fission (Bielli et al, 2005;Lee et al, 2005;Drin and Antonny, 2010;Boucrot et al, 2012;Schwieger et al, 2017). Work from several laboratories has provided crucial structural insights into how Sec7-domain Arf-GEFs exchange nucleotide, and models for how Sec7domain Arf-GEFs with pleckstrin homology domains are organized on the membrane surface (Cherfils et al, 1998;Goldberg, 1998;Renault et al, 2003;DiNitto et al, 2007;Aizel et al, 2013;Malaby et al, 2013;Padovani et al, 2014;Galindo et al, 2016;Richardson et al, 2016;Karandur et al, 2017;Das et al, 2019). However, it remains unclear whether the Sec7 domain itself interacts directly with the membrane, and a detailed mechanistic description of how Arf-GEFs deal with insertion of the substrate amphipathic a helix has not been reported.…”