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Structural Basis of Membrane Curvature Recognition by the ALPS Motifs

Abstract : The recruitment of many cytosolic factors is regulated by the lipid composition but also by the shape of organelles membrane. Ten years ago, we identified in ArfGAP1 a motif of 30 amino-acids termed ALPS that allows this protein to detect the positive curvature of the COPI vesicles at the end of their biogenesis and to trigger the depolymerisation of coat proteins wrapping these vesicles. We found that the ALPS motif folds into a peculiar amphipathic helix whose insertion into membrane depends on defects in lipid-packing induced by curvature. ALPS motifs were next identified in various proteins such as GMAP-210, a membrane tethering factor, or Osh4p, a sterol/PI(4)P exchanger. Different studies illustrated how membrane curvature regulates the activity of these proteins. At a more atomistic level, we gained results that explain why the ALPS motif is so sensitive to lipid-packing defects and membrane curvature. We first indicated that the lack of basic residues in the polar face of the ALPS motif explains its sensitivity to curvature of cellular membrane. Next, molecular dynamic simulations suggested that the insertion of the ALPS motif, solely mediated by the insertion of bulk hydrophobic residue, directly depends on the pre-existence of lipid-packing defects in membrane. More recently, NMR studies in a membrane environment showed that the ALPS motif of ArfGAP1 folds into a helix displaying a not well-defined central region between two helical fragments. The stability of ALPS helix was also assessed by replica-exchange molecular dynamics simulations. Jointly, these results suggest that the sequence of an ALPS motif codes for a loose and non-canonical amphipathic helix whose features are perfectly well adapted for responding to change in membrane curvature
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Contributor : Laurent Jonchère Connect in order to contact the contributor
Submitted on : Wednesday, December 9, 2015 - 1:37:42 PM
Last modification on : Friday, December 10, 2021 - 3:52:10 PM

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Liza Mouret, Lydie Vamparys, Joachim Moser von Filseck, Patrick Fuchs, Arnaud Bondon, et al.. Structural Basis of Membrane Curvature Recognition by the ALPS Motifs. Biophysical Journal, Biophysical Society, 2015, 108 (2), pp.2. ⟨10.1016/j.bpj.2014.11.026⟩. ⟨hal-01240649⟩



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