Abstract
It is known that membrane proteins are important in various secretory pathways, with a possible role of their transmembrane domains (TMDs) as sorting determinant factors. One key aspect of TMDs associated with various “checkposts” (i.e. organelles) of intracellular trafficking is their length. To explore possible linkages in organisms with varying “complexity” and differences in TMD lengths of membrane proteins associated with different organelles (such as Endoplasmic Reticulum, Golgi, Endosomes, Nucleus, Plasma Membrane), we analyzed ~70000 membrane protein sequences in over 300 genomes of fungi, plants, non-mammalian vertebrates and mammals. We report that as we move from simpler to complex organisms, variation in organellar TMD lengths decreases, especially compared to their respective plasma membranes, with increasing organismal complexity. This suggests an evolutionary pressure in modulating length of TMDs of membrane proteins with increasing complexity of communication between sub-cellular compartments. We also report functional applications of our findings by discovering remarkable distinctions in TMD lengths of membrane proteins associated with different intracellular transport pathways. Finally, we show that TMD lengths extracted from viral proteins can serve as somewhat weak indicators of viral replication sites in plant cells but very strong indicators of different entry pathways employed by animal viruses.
Highlights
Membrane protein sequences corresponding to 301 genomes of fungi, plants, non-mammalian vertebrates and mammals
The first remarkable result we report in this work, while confirming the original findings of Sharpe et al.[11] for fungi and vertebrates, is a decrease in variation of transmembrane domains (TMDs) lengths of membrane proteins with increasing organismal complexity
The key hypothesis to test was that TMD lengths of viral proteins may provide signatures of subcellular locations of internalization- or secretory- or replication- pathways associated with their life cycles in respective host cells
Summary
Membrane protein sequences corresponding to 301 genomes of fungi, plants, non-mammalian vertebrates and mammals. The fact that we were able to confirm and substantially generalize that TMD lengths serve as signatures for subcellular locations in different eukaryotic systems, we decided to further explore the scope of our findings from an extremely important applicational perspective Viruses in both animals and plants, regardless of presence[12,13,14,15,16] or absence of a membrane envelope, rely heavily on intracellular trafficking and sorting[17] mechanisms of their host cells, including viral replication associated with host intracellular membranes[18]. We analyzed experimentally determined viral protein sequences that are known to play a key role in their entry (in case of animal viruses), and replication (in case of plant viruses), into their respective hosts – serving as strong experimentally determined controls for our analyses With this approach, we report that TMD lengths of viral proteins do serve as signatures for important host cell “checkposts” (i.e. membrane/ organellar host cell locations) involved in life cycles of both animal and plant viruses. This work opens up a very promising avenue for designing experiments aimed at interfering with viral transport mechanisms for both animal and plant viruses using a relatively straightforward, yet rigorous and somewhat computationally economical, analytical approach
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