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MARCKS-ED Peptide as a Curvature and Lipid Sensor

Leslie A. Morton , Hengwen Yang , Jonel P. Saludes , Zeno Fiorini , Lida Beninson , Edwin R. Chapman , Monika Fleshner , Ding Xue , and Hang Yin

ACS Chem. Biol., Just Accepted Manuscript
DOI: 10.1021/cb300429e
Publication Date (Web): October 17, 2012
Copyright © 2012 American Chemical Society

Membrane curvature and lipid composition regulates important biological processes within a cell. Currently, several proteins have been reported to sense and/or induce membrane curvatures, e.g. Synaptotagmin-1 and Amphiphysin. However, the large protein scaffold of these curvature sensors limits their applications in complex biological systems. Our interest focuses on identifying and designing peptides that can sense membrane curvature based on established elements observed in natural curvature-sensing proteins. Membrane curvature remodeling also depends on their lipid composition, suggesting strategies to specifically target membrane shape and lipid components simultaneously. We have successfully identified a 25-mer peptide, MARCKS-ED, based on the effector domain sequence of the intracellular membrane protein myristoylated alanine-rich C-kinase substrate that can recognize PS with preferences for highly curved vesicles in a sequence specific manner. These studies further contribute to the understanding of how proteins and peptides sense membrane curvature, as well as provide potential probes for membrane shape and lipid composition.