Role of Model Proteins on Membrane Fusion

Abstract

Within neural cells, synaptic vesicles carry neurotransmitters (signaling molecule) through the plasma membrane. In order to do so synaptic vesicles must fuse with the plasma membrane, so that the enclosed neurotransmitter can cross it. Typically, without fusion proteins membrane fusion occurs on a very long time scale. However, it has been established that the fusion occur via fusion proteins (FPs), which initially are bound to one or both of the fusing membranes via a trans-membrane (TM) helix, utilize energetically favorable conformational transitions to lower the activation energy for membrane fusion, and thus are key participants in shaping the energy landscape by facilitating bilayer-bilayer apposition and dehydration as bilayers come into more intimate contact. It is also widely accepted that the trans-membrane (TM) part of the FPs has vital role in governing the fusion, fusion does not occur if TM is replaced with lipid molecules. In order to understand how the TM segment of FPs facilitates membrane fusion, we used a model protein that mimics mostly the TM part of the FPs, of similar dimensions to an α-helix. In doing so, the length of the model protein was chosen to match the thickness of a POPC bilayer. To retain the trans-membrane orientation of the model proteins without adding the soluble domains, we truncated the ends with polar groups. The middle portion was kept non-polar. We observed via coarse-grained molecular dynamics simulations that the self-aggregation of the model proteins greatly enhances the rate of formation of hemi-fused intermediate states. Also, the model-proteins if present in relatively higher concentration drive the attachment of a 20nm size vesicle to a flat bilayer.