Abstract
BAR superfamily domains shape membranes through poorly understood mechanisms. We solved structures of F-BAR modules bound to flat and curved bilayers using electron (cryo)microscopy. We show that membrane tubules form when F-BARs polymerize into helical coats that are held together by lateral and tip-to-tip interactions. On gel-state membranes or after mutation of residues along the lateral interaction surface, F-BARs adsorb onto bilayers via surfaces other than their concave face. We conclude that membrane binding is separable from membrane bending, and that imposition of the module's concave surface forces fluid-phase bilayers to bend locally. Furthermore, exposure of the domain's lateral interaction surface through a change in orientation serves as the crucial trigger for assembly of the helical coat and propagation of bilayer bending. The geometric constraints and sequential assembly of the helical lattice explain how F-BAR and classical BAR domains segregate into distinct microdomains, and provide insight into the spatial regulation of membrane invagination.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 807-817 |
| Number of pages | 11 |
| Journal | Cell |
| Volume | 132 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 7 2008 |
Funding
We thank Derek Toomre for his direction with the live cell imaging experiments. We thank Bridget Carragher and the staff at the National Resource for Automated Molecular Microscopy—which is supported by the National Institutes of Health (NIH) through the National Center for Research Resources (NCRR) P41 program (RR17573)—where some of the data was collected. We thank Toshiki Itoh for discussion during the initial stages of this project. We also thank Robert Bjornson and Nicholas Carriero at the Yale Center for High Performance Computation in Biology and Biomedicine, which is supported by NIH grant NCRR 19895-02. Finally, we thank Fred Sigworth and David Chester for their advice and helpful discussions. This work was supported by a Predoctoral Research Training Fellowship from the Epilepsy Foundation (A.F.); the European Molecular Biology Organization Long-Term Postdoctoral Fellowship program and the Cross-Disciplinary Fellowship program of the Human Frontier Science Program (A.R.); and a G. Harold and Leila Y. Mathers Charitable Foundation grant (P.D.C). This work was also supported in part by the following NIH grants: MSTP TG 5T32GM07205 (A.F.), GM071590 and DA024101 (V.M.U), EB001567 (E.H.E.), CA46128, and DK45735 (P.D.C).
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology