Membrane fusion proteins (SNARE complex)

Membrane fusion proteins (SNARE complex)

The SNARE (Soluble N-ethylmaleimide-sensitive factor Attachment protein Receptor) proteins play a central role in membrane fusion in the cell, and in particular in the exocytosis of synaptic vesicles at nerve ending, mediating the fusion of vesicles with plasma membrane to release neurotransmitter for synaptic transmission.  The neuronal SNAREs consist of the syntaxin 1 and SNAP-25 proteins in the plasma membrane (t-SNARE, from target), and the synaptobrevin (also called VAMP2 protein) in the vesicle membrane (v-SNARE, from vesicle). The SNARE´s complex formed by those three proteins forms a parallel four-helix bundle, that is thought to drive the membrane fusion via a zippering process toward the membrane, exerting mechanical force on the membrane that overcomes an estimated energy barrier of >40 kBT.

SMFS represents an unique tool to describe the SNAREs proteins behavior by directly measuring the forces and the kinetics of the process of assembling-disassembling the SNARE complex. Although SMFS studies have been performed in SNAREs proteins, a single molecule marker based study that do not directly perturb the proteins is lacked. In the Protein Nanomechanics Lab we are developing a polyprotein single molecule strategy that will allow us to measure the mechanics of SNARE´s proteins without disturbing it.

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