Abstract
The Golgi-associated protein ArfGAP1 has an unusual membrane-adsorbing amphipathic α-helix: its polar face is weakly charged, containing mainly serine and threonine residues. We show that this feature explains the specificity of ArfGAP1 for curved versus flat lipid membranes. We built an algorithm to identify other potential amphipathic α-helices rich in serine and threonine residues in protein databases. Among the identified sequences, we show that three act as membrane curvature sensors. In the golgin GMAP-210, the sensor may serve to trap small vesicles at the end of a long coiled coil. In Osh4p/Kes1p, which transports sterol between membranes, the sensor controls access to the sterol-binding pocket. In the nucleoporin Nup133, the sensor corresponds to an exposed loop of a β-propeller structure. Ser/Thr-rich amphipathic helices thus define a general motif used by proteins of various functions for sensing membrane curvature.
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Acknowledgements
We thank M. Bornens (Institut Curie), R.M. Rios (Universidad de Sevilla) and V.A. Bankaitis (University of North Carolina) for the GMAP-210 and Kes1p plasmids, S. Scarzello for mass spectrometry analysis, N. Leroudier for DNA sequencing and V. Morello for help with experiments. We also thank M. Bornens, M. Chabre, B. Goud, C. Jackson, S. Paris and members of our laboratories for discussions. This work was supported by the CNRS, the Ministère de la Recherche (Action Concertée Incitative: dynamique et réactivité des assemblages biologiques) and by the Agence Nationale de la Recherche (ANR non thématique). G.D. was supported by postdoctoral fellowships from the CNRS and the ANR.
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G.D. and B.A. conceived the study and wrote the manuscript. G.D. and J.-F.C. prepared most protein constructs and performed the biochemical experiments. G.D. performed the spectroscopic measurements. R.G. conceived the bioinformatics program. T.B. and T.U.S. designed and prepared the Nup133 constructs.
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Supplementary information
Supplementary Table 1
Human proteins with a putative ALPS-like motif. (PDF 231 kb)
Supplementary Table 2
Yeast proteins with a putative ALPS-like motif. (PDF 217 kb)
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Drin, G., Casella, JF., Gautier, R. et al. A general amphipathic α-helical motif for sensing membrane curvature. Nat Struct Mol Biol 14, 138–146 (2007). https://doi.org/10.1038/nsmb1194
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DOI: https://doi.org/10.1038/nsmb1194
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