Comparison of In Silico Signal Sequence-Phospholipid Results with Described In Vitro and In Vivo Protein Translocation Studies Seems to Underscore the Significance of Phospholipids

Abstract

The precise role of protein–lipid interactions in protein translocation is, after almost four decades of research, still a matter of debate. The experimental evidence, as described in the literature, indicates that (anionic) phospholipids play a role in numerous events in protein translocation; however, its meaning and relevance are still a matter of debate. This study tries to fill some missing links in the experimental evidence by means of in silico experiments. The study presented here indicates not only that there is a direct signal sequence–phospholipid interaction but also that the corresponding signal peptides can translocate additional amino acids across a pure lipid membrane. Furthermore, results are presented when it comes to the extent of anionic phospholipids’ dependence on this process. The correlations between the in silico results of pure signal peptide–phospholipid interactions and the observed experimental trends in the overall protein translocation effects are at least remarkable. The results emphasize that new models for protein translocation will have to be developed to take all these and previous experimental data into account.