Article abstract


Nature Chemical Biology 5, 835 - 841 (2009)
Published online: 13 September 2009 | doi:10.1038/nchembio.213

How curved membranes recruit amphipathic helices and protein anchoring motifs

Nikos S Hatzakis1,5, Vikram K Bhatia1,5, Jannik Larsen1, Kenneth L Madsen2, Pierre-Yves Bolinger1,4, Andreas H Kunding1, John Castillo1,4, Ulrik Gether2, Per Hedegård3 & Dimitrios Stamou1


Lipids and several specialized proteins are thought to be able to sense the curvature of membranes (MC). Here we used quantitative fluorescence microscopy to measure curvature-selective binding of amphipathic motifs on single liposomes 50–700 nm in diameter. Our results revealed that sensing is predominantly mediated by a higher density of binding sites on curved membranes instead of higher affinity. We proposed a model based on curvature-induced defects in lipid packing that related these findings to lipid sorting and accurately predicted the existence of a new ubiquitous class of curvature sensors: membrane-anchored proteins. The fact that unrelated structural motifs such as alpha-helices and alkyl chains sense MC led us to propose that MC sensing is a generic property of curved membranes rather than a property of the anchoring molecules. We therefore anticipate that MC will promote the redistribution of proteins that are anchored in membranes through other types of hydrophobic moieties.

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  1. Bio-Nanotechnology Laboratory, Department of Neuroscience and Pharmacology & Nano-Science Center, University of Copenhagen, Copenhagen, Denmark.
  2. Molecular Neuropharmacology Group and Center for Pharmacogenomics, Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark.
  3. Nano-Science Center, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
  4. Present addresses: Credit Suisse, Zürich, Switzerland (P.-Y.B.); School of Chemistry, Industrial University of Santander, Bucaramanga, Colombia (J.C.).
  5. These authors contributed equally to this work.

Correspondence to: Dimitrios Stamou1 e-mail: stamou@nano.ku.dk



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