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


Bin/Amphiphysin/Rvs (BAR) domain proteins control the curvature of lipid membranes in endocytosis, trafficking, cell motility, the formation of complex subcellular structures, and many other cellular phenomena. They form 3D assemblies that 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 use 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 of the United States of America
Issue number40
Publication statusPublished - 4 Oct 2016
Externally publishedYes


  • BAR proteins
  • Endocytosis
  • Membrane curvature
  • Protein scaffold
  • Self-assembly


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