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Angew Chem Int Ed Engl. 2015 Nov 23;54(48):14388-92. doi: 10.1002/anie.201506844. Epub 2015 Oct 6.

Accelerating SNARE-Mediated Membrane Fusion by DNA-Lipid Tethers.

Xu W1,2, Wang J1,2, Rothman JE3,4, Pincet F5,6,7.

Author information

1
Nanobiology Institute, Yale University, West Haven, CT 06516 (USA).
2
Yale University, Department of Cell Biology, School of Medicine, New Haven, CT 06511 (USA).
3
Nanobiology Institute, Yale University, West Haven, CT 06516 (USA). james.rothman@yale.edu.
4
Yale University, Department of Cell Biology, School of Medicine, New Haven, CT 06511 (USA). james.rothman@yale.edu.
5
Nanobiology Institute, Yale University, West Haven, CT 06516 (USA). pincet@lps.ens.fr.
6
Yale University, Department of Cell Biology, School of Medicine, New Haven, CT 06511 (USA). pincet@lps.ens.fr.
7
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.

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.

KEYWORDS:

liposomes; membrane fusion; membrane proteins; protein mimics; ssDNA-lipid conjugation

PMID:
26439984
PMCID:
PMC4888371
DOI:
10.1002/anie.201506844
[Indexed for MEDLINE]
Free PMC Article
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