title: Accelerating SNARE-Mediated Membrane Fusion by DNA-Lipid Tethers.
abstract: SNARE proteins are the core machinery to drive fusion of a vesicle with its target membrane. Inspired by the tethering proteins that bridge the membranes and thus prepare SNAREs for docking and fusion, we developed a lipid-conjugated ssDNA mimic that is capable of regulating SNARE function, in situ. The DNA-lipid tethers consist of a 21 base pairs binding segment at the membrane distal end that can bridge two liposomes via specific base-pair hybridization. A linker at the membrane proximal end is used to control the separation distance between the liposomes. In the presence of these artificial tethers, SNARE-mediated lipid mixing is significantly accelerated, and the maximum fusion rate is obtained with the linker shorter than 40 nucleotides. As a programmable tool orthogonal to any native proteins, the DNA-lipid tethers can be further applied to regulate other biological processes where capturing and bridging of two membranes are the prerequisites for the subsequent protein function.
authors.affiliation: Nanobiology Institute, Yale University, West Haven, CT 06516 (USA).|Yale University, Department of Cell Biology, School of Medicine, New Haven, CT 06511 (USA).
authors.forename: Weiming
authors.initials: W
authors.lastname: Xu
authors.affiliation: Nanobiology Institute, Yale University, West Haven, CT 06516 (USA).|Yale University, Department of Cell Biology, School of Medicine, New Haven, CT 06511 (USA).
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Nanobiology Institute, Yale University, West Haven, CT 06516 (USA). james.rothman@yale.edu.|Yale University, Department of Cell Biology, School of Medicine, New Haven, CT 06511 (USA). james.rothman@yale.edu.
authors.forename: James E
authors.initials: JE
authors.lastname: Rothman
authors.affiliation: Nanobiology Institute, Yale University, West Haven, CT 06516 (USA). pincet@lps.ens.fr.|Yale University, Department of Cell Biology, School of Medicine, New Haven, CT 06511 (USA). pincet@lps.ens.fr.|Laboratoire de Physique Statistique, Ecole Normale Supérieure de Paris, Université Pierre et Marie Curie, Université Paris Diderot, Centre National de la Recherche Scientifique, Paris, 75005 (France). pincet@lps.ens.fr.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pincet
mesh_terms: D004247:DNA / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D008561:Membrane Fusion / Q000502:physiology*; D050600:SNARE Proteins / Q000502:physiology*
chemical_list: D008055:Lipids; D050600:SNARE Proteins; D004247:DNA
keywords: liposomes; membrane fusion; membrane proteins; protein mimics; ssDNA-lipid conjugation