NSP6 (rotavirus)
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Putative transmembrane domain more commonly known as Non-structural Protein 6 (NSP6) is one of the two non-structural proteins that gene 11 in
rotavirus ''Rotavirus'' is a genus of double-stranded RNA viruses in the family ''Reoviridae''. Rotaviruses are the most common cause of diarrhoeal disease among infants and young children. Nearly every child in the world is infected with a rotavirus ...
encodes for alongside NSP5. NSP6 is composed of six
transmembrane domain A transmembrane domain (TMD) is a membrane-spanning protein domain. TMDs generally adopt an alpha helix topological conformation, although some TMDs such as those in porins can adopt a different conformation. Because the interior of the lipid bi ...
s and a C terminal tail. In contrast to the other rotavirus non-structural proteins, NSP6 was found to have a high rate of turnover, being completely degraded within 2 hours of synthesis. NSP6 was found to be a sequence-independent nucleic acid binding protein, with similar affinities for ssRNA and
dsRNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
It has been determined that NSP6 has three crucial functions that it conducts. As messages flow among the replication organelle and the endoplasmic reticulum (ER) NSP6 acts as a filter. In this case, NSP6 hinders the access of ER luminal proteins to the DMVs but permits the passing of
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...
s. Next NSP6 arranges DMV clusters, since the DMV clusters are organized by NSP6 it can reconstruct them with LD-derived Lipids. Lastly, through LD-tethering complex DFCP1-RAB18 intervenes in the contact of
lipid droplet Lipid droplets, also referred to as lipid bodies, oil bodies or adiposomes, are lipid-rich cellular organelles that regulate the storage and hydrolysis of neutral lipids and are found largely in the adipose tissue. They also serve as a reservoi ...
s (LDs). Since NSP6 is one of two non-structural proteins that gene 11 codes for NSP6 is found in both α and β coronaviruses and produces
autophagosome An autophagosome is a spherical structure with double layer membranes. It is the key structure in macroautophagy, the intracellular degradation system for cytoplasmic contents (e.g., abnormal intracellular proteins, excess or damaged organelles, i ...
s. While NSP6 is found to produce a substantial amount of autophagosomes, through the analysis of
MAP1LC3B Microtubule-associated proteins 1A/1B light chain 3B (hereafter referred to as LC3) is a protein that in humans is encoded by the ''MAP1LC3B'' gene. LC3 is a central protein in the autophagy pathway where it functions in autophagy substrate selec ...
puncta it is observed that autophagosomes produced by NSP6 are much smaller in size. As indicated by the statistical analysis of WIPI2 puncta the size of NSP6-produced autophagosomes is restricted at
omegasome ] Omegasome is a Cell (biology), cell organelle consisting of lipid bilayer Biological membrane, membranes enriched for phosphatidylinositol 3-phosphate (abbreviated PI(3)P or PtdIns3P), and related to a process of autophagy. It is a subdomain of t ...
formation. The small size of these autophagosomes inhibits the transportation of viral components to
lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane pr ...
s and this could aid in coronavirus infection.


References

{{Viral proteins Rotaviruses Viral nonstructural proteins