SNARE motif: A common motif used by pathogens to manipulate membrane fusion

Abstract

To penetrate host cells through their membranes, pathogens use a variety of molecular components in which the presence of heptad repeat motifs seems to be a prevailing element. Heptad repeats are characterized by a pattern of seven, generally hydrophobic, residues. In order to initiate membrane fusion, viruses use glycoproteins-containing heptad repeats. These proteins are structurally and functionally similar to the SNARE proteins known to be involved in eukaryotic membrane fusion. SNAREs also display a heptad repeat motif called the "SNARE motif". As bacterial genomes are being sequenced, microorganisms also appear to be carrying membrane proteins resembling eukaryotic SNAREs. This category of SNARE-like proteins might share similar functions and could be used by microorganisms to either promote or block membrane fusion. Such a recurrence across pathogenic organisms suggests that this architectural motif was evolutionarily selected because it most effectively ensures the survival of pathogens within the eukaryotic environment.

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Acknowledgements

We thank the members of the Paumet laboratory, especially Benjamin Scheinfeld, for technical assistance in the project. We are grateful to Dr. James McNew (Rice University, TX) for critical reading of the manuscript and helpful discussion. This research is supported by the National Institutes of Health grant # RO1 AI073486 (to F.P.).

Figures and Tables

Figure 1 Eukaryotic SNAREs and viral coiled-coil proteins trigger membrane fusion. (A) During a fusion event in eukaryotic cells, the t-SNAREs present on the target membrane interact with the v-SNAREs present on the vesicle. This interaction brings both membranes into a close apposition and leads to membrane fusion. (B) During a viral infection, enveloped viruses enter their host cells through fusion with the host membrane (plasma membrane or endosome membrane). For example, HIV envelope protein gp41 utilizes three α-helical domains, which collapse into a trimer of hairpins to facilitate fusion between the host plasma membrane and the viral envelope thereby providing its viral contents access to the host cytosol.

Figure 2 Bacterial coiled-coil proteins inhibit membrane fusion (working model). Left: Non-pathogenic bacteria (blue) are internalized. Normal phagosome maturation is initiated and results in lysosomal fusion (formation of phagolysosomes) and destruction of the phagosomal content. Right: Intracellular bacteria (red) are internalized and express their own proteins on the surface of the phagosome (red coiled-coil proteins), blocking its maturation.

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