TABLE 2.
Examples of lipid cofactors of fission-inducing proteins containing amphipathic helices.
| Protein | Lipid cofactors | Membrane interaction | Generation of membrane curvature | Topology of fission |
| Epsin | PtdIns(4,5)P2 | H0 of epsin interacts with PtdIns(4,5)P2- containing, but not with PS-containing liposomes (Kweon et al., 2006) | Vesiculation occurs on PtdIns(4,5)P2-containing membranes but not on PS-containing membranes (Boucrot et al., 2012) | Normal |
| Mammalian amphiphysin 2 | PtdIns(4,5)P2 | Binds specifically to liposomes containing PtdIns(4,5)P2 and to lesser extent PtdIns4P, but not PS, PtdIns, PtdIns(3,4)P2, PtdIns(3,5)P2 (Lee et al., 2002) | Tubulation and vesiculation were observed on PtdIns(4,5)P2-containing liposomes, but to a much lesser extent on PtdIns(4,5)P2-free liposomes (Wu and Baumgart, 2014) | Normal |
| Drosophila amphiphysin | PtdIns(4,5)P2 | Binds specifically to vesicles containing PtdIns(4,5)P2 and PtdIns(3,4,5)P3 but not other PtdInsPs (Yoon et al., 2012) | Tubulation requires PtdIns(4,5)P2, but not PS (Yoon et al., 2012) | Normal |
| Endophilin A1 | PtdIns(4,5)P2 | Binds specifically to vesicles containing PtdIns(4,5)P2 and PtdIns(3,4,5)P3, but not other PtdInsPs (Yoon et al., 2012) | Tubulation requires PtdIns(4,5)P2, but not PS (Yoon et al., 2012) | Normal |
| AtPmtA (bacterial) | CL and MMPE | Binds to cardiolipin-containing liposomes, but poorly to PA-containing liposomes (Danne et al., 2017b) | Tubulation was observed on CL-containing liposomes, but with less efficacy on PG-, PtdIns4P-, and PA-containing liposomes. The addition of MMPE to CL-containing liposomes bound to PmtA promotes vesiculation (Danne et al., 2017b) | Normal |
| Atg18 from yeast | PtdIns3P and PtdIns(3,5)P2 | Binds to PtdIns3P-containing and PtdIns(3,5)P2-containing liposomes. Does not bind to PtdIns(4,5)P2-containing or PS-containing liposomes (Gopaldass et al., 2017) | Vesiculation occurs on GUVs containing PtdIns3P and PtdIns(3,5)P2. Scission was not observed on GUVs containing PtdIns(4,5)P2 (Gopaldass et al., 2017) | Normal |
| M2 from influenza virus | Cholesterol | M2 binds cholesterol specifically (Ekanayake et al., 2016; Elkins et al., 2017, 2018) | Cholesterol significantly augmented the capability of the M2 amphipathic helix (M2AH) in inducing bilayer pits. POPG does not have the ability of significantly impacting M2AH-induced membrane modulation (Pan et al., 2019) | Reverse |
The indicated lipids are specifically required for membrane fission reactions mediated by these proteins. Other lipids cannot replace these lipid cofactors to generate membrane curvature (i.e., tubulation and vesiculation). The topology of fission reaction for each protein is also shown.