Structure
Volume 23, Issue 5, 5 May 2015, Pages 873-881
Journal home page for Structure

Article
Tubulation by Amphiphysin Requires Concentration-Dependent Switching from Wedging to Scaffolding

https://doi.org/10.1016/j.str.2015.02.014Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Amphiphysin uses helical wedges and not its BAR domain for vesicle interaction

  • Amphiphysin uses oligomeric BAR domains to scaffold membrane tubes

  • Formation of oligomeric scaffolds on tubes requires a threshold protein concentration

  • Membrane insertion pocket of the BAR domain is the site of numerous disease mutants

Summary

BAR proteins are involved in a variety of membrane remodeling events but how they can mold membranes into different shapes remains poorly understood. Using electron paramagnetic resonance, we find that vesicle binding of the N-BAR protein amphiphysin is predominantly mediated by the shallow insertion of amphipathic N-terminal helices. In contrast, the interaction with tubes involves deeply inserted N-terminal helices together with the concave surface of the BAR domain, which acts as a scaffold. Combined with the observed concentration dependence of tubulation and BAR domain scaffolding, the data indicate that initial membrane deformations and vesicle binding are mediated by insertion of amphipathic helical wedges, while tubulation requires high protein densities at which oligomeric BAR domain scaffolds form. In addition, we identify a pocket of residues on the concave surface of the BAR domain that insert deeply into tube membrane. Interestingly, this pocket harbors a number of disease mutants in the homologous amphiphysin 2.

Cited by (0)

3

Co-first author