Amphipathic motifs in BAR domains are essential for membrane curvature sensing

Publication: Research - peer-reviewJournal article – Annual report year: 2009

Without internal affiliation

  • Author: Bhatia, Vikram K.

    University of Copenhagen

  • Author: Madsen, Kenneth L.

    University of Copenhagen

  • Author: Bolinger, Pierre-Yves

    University of Copenhagen

  • Author: Kunding, Andreas Hjarne

    University of Copenhagen

  • Author: Hedegård, Per

    University of Copenhagen

  • Author: Gether, Ulrik

    University of Copenhagen

  • Author: Stamou, Dimitrios

    University of Copenhagen

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BAR (Bin/Amphiphysin/Rvs) domains and amphipathic a-helices (AHs) are believed to be sensors of membrane curvature thus facilitating the assembly of protein complexes on curved membranes. Here, we used quantitative fluorescence microscopy to compare the binding of both motifs on single nanosized liposomes of different diameters and therefore membrane curvature. Characterization of members of the three BAR domain families showed surprisingly that the crescent-shaped BAR dimer with its positively charged concave face is not able to sense membrane curvature. Mutagenesis on BAR domains showed that membrane curvature sensing critically depends on the N-terminal AH and furthermore that BAR domains sense membrane curvature through hydrophobic insertion in lipid packing defects and not through electrostatics. Consequently, amphipathic motifs, such as AHs, that are often associated with BAR domains emerge as an important means for a protein to sense membrane curvature. Measurements on single liposomes allowed us to document heterogeneous binding behaviour within the ensemble and quantify the influence of liposome polydispersity on bulk membrane curvature sensing experiments. The latter results suggest that bulk liposome-binding experiments should be interpreted with great caution.
Keyword: Single liposomes,BAR domain,Amphipathic a-helix,Membrane insertion,Membrane curvature sensing
Original languageEnglish
JournalE M B O Journal
Publication date2009
Volume28
Pages3303-3314
ISSN0261-4189
DOIs
StatePublished
CitationsWeb of Science® Times Cited: 87
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