BAR scaffolds drive membrane fission by crowding disordered domains

Wilton T. Snead; Wade F. Zeno; Grace Kago; Ryan W. Perkins; J Blair Richter; Chi Zhao; Eileen M. Lafer; Jeanne C. Stachowiak

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/276147 doi: bioRxiv preprint of I-BAR-AP180 CTD that we tested, 5 µM, drove membrane fission, generating a population of vesicles centered near 30 nm diameter (Fig. 5D ). This result demonstrates that, under appropriate conditions, steric pressure among crowded disordered domains is sufficient to overcome the structure-based curvature preference of the I-BAR scaffold. Importantly, while wild-type IRSp53 does not naturally contain a large disordered domain, the I-BAR domain-containing proteins MIM and ABBA do contain regions of substantial disorder (approximately 475 amino acids in MIM) (Lee et al., 2007) . Therefore, our observations raise the question of whether the presumed role of these proteins in driving cellular membrane protrusions can be justified on the basis of in vitro studies of their isolated I-BAR domains (Mattila et al., 2007; Saarikangas et al., 2009 ).