How curvature-generating proteins build scaffolds on membrane nanotubes

Mijo Simunovic, Emma Evergren, Ivan Golushko, Coline Prévost, Henri-François Renard, Ludger Johannes, Harvey T McMahon, Vladimir Lorman, Gregory A Voth, Patricia Bassereau

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)
152 Downloads (Pure)


Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex sub-cellular structures, and many other cellular phenomena. They form three-dimensional assemblies, which act as molecular scaffolds to reshape the membrane and alter its mechanical properties. It is unknown, however, how a protein scaffold forms and how BAR domains interact in these assemblies at protein densities relevant for a cell. In this work, we employ various experimental, theoretical and simulation approaches to explore how BAR proteins organize to form a scaffold on a membrane nanotube. By combining quantitative microscopy with analytical modeling, we demonstrate that a highly curving BAR protein endophilin nucleates its scaffolds at the ends of a membrane tube, contrary to a weaker curving protein centaurin, which binds evenly along the tube’s length. Our work implies that the nature of local protein-membrane interactions can affect the specific localization of proteins on membrane-remodeling sites. Furthermore, we show that amphipathic helices are dispensable in forming protein scaffolds. Finally, we explore a possible molecular structure of a BAR-domain scaffold using coarse-grained molecular dynamics simulations. Together with fluorescence microscopy, the simulations show that proteins need only to cover 30–40% of a tube’s surface to form a rigid assembly. Our work provides mechanical and structural insights into the way BAR proteins may sculpt the membrane as a high-order cooperative assembly in important biological processes. 
Original languageEnglish
Pages (from-to)11226-11231
Number of pages6
JournalProceedings of the National Academy of Sciences
Issue number40
Publication statusPublished - 04 Oct 2016

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