NSP6 (rotavirus)
Identifiers
SymbolRota_NS6
PfamPF04866
InterProIPR006950
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

Putative transmembrane domain [1] more commonly known as Non-structural Protein 6 (NSP6) is one of the two non-structural proteins that gene 11 in rotavirus encodes for alongside NSP5.[2] NSP6 is composed of six transmembrane domains and a C terminal tail.[3] 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[4]

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 lipids. 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 droplets (LDs).[5]

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 autophagosomes.[6] While NSP6 is found to produce a substantial amount of autophagosomes, through the analysis of MAP1LC3B 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 formation. The small size of these autophagosomes inhibits the transportation of viral components to lysosomes and this could aid in coronavirus infection.[7]

References

  1. ^ Yadav, Rohitash; Chaudhary, Jitendra Kumar; Jain, Neeraj; Chaudhary, Pankaj Kumar; Khanra, Supriya; Dhamija, Puneet; Sharma, Ambika; Kumar, Ashish; Handu, Shailendra (2021-04-06). "Role of Structural and Non-Structural Proteins and Therapeutic Targets of SARS-CoV-2 for COVID-19". Cells. 10 (4): 821. doi:10.3390/cells10040821. ISSN 2073-4409. PMC 8067447. PMID 33917481.
  2. ^ Komoto, Satoshi; Kanai, Yuta; Fukuda, Saori; Kugita, Masanori; Kawagishi, Takahiro; Ito, Naoto; Sugiyama, Makoto; Matsuura, Yoshiharu; Kobayashi, Takeshi; Taniguchi, Koki (November 2017). "Reverse Genetics System Demonstrates that Rotavirus Nonstructural Protein NSP6 Is Not Essential for Viral Replication in Cell Culture". Journal of Virology. 91 (21): e00695-17. doi:10.1128/JVI.00695-17. ISSN 0022-538X. PMC 5640853. PMID 28794037.
  3. ^ Baliji, Surendranath; Cammer, Stephen A; Sobral, Bruno; Baker, Susan C (2009-07-01). "Detection of nonstructural protein 6 in murine coronavirus-infected cells and analysis of the transmembrane topology by using bioinformatics and molecular approaches". Journal of Virology. 83 (13): 6957–6962. doi:10.1128/jvi.00254-09. ISSN 1098-5514. PMC 2698535. PMID 19386712.
  4. ^ Rainsford, Edward W.; McCrae, Malcolm A. (2007-12-01). "Characterization of the NSP6 protein product of rotavirus gene 11". Virus Research. 130 (1): 193–201. doi:10.1016/j.virusres.2007.06.011. ISSN 0168-1702. PMID 17658646.
  5. ^ Ricciardi, Simona; Guarino, Andrea Maria; Giaquinto, Laura; Polishchuk, Elena V.; Santoro, Michele; Di Tullio, Giuseppe; Wilson, Cathal; Panariello, Francesco; Soares, Vinicius C.; Dias, Suelen S. G.; Santos, Julia C.; Souza, Thiago M. L.; Fusco, Giovanna; Viscardi, Maurizio; Brandi, Sergio (June 2022). "The role of NSP6 in the biogenesis of the SARS-CoV-2 replication organelle". Nature. 606 (7915): 761–768. Bibcode:2022Natur.606..761R. doi:10.1038/s41586-022-04835-6. ISSN 1476-4687. PMC 7612910. PMID 35551511.
  6. ^ Benvenuto, Domenico; Angeletti, Silvia; Giovanetti, Marta; Bianchi, Martina; Pascarella, Stefano; Cauda, Roberto; Ciccozzi, Massimo; Cassone, Antonio (July 2020). "Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy". Journal of Infection. 81 (1): e24–e27. doi:10.1016/j.jinf.2020.03.058. ISSN 0163-4453. PMC 7195303. PMID 32283146.
  7. ^ Cottam, Eleanor M; Whelband, Matthew C; Wileman, Thomas (2014-08-01). "Coronavirus NSP6 restricts autophagosome expansion". Autophagy. 10 (8): 1426–1441. doi:10.4161/auto.29309. ISSN 1554-8627. PMC 4203519. PMID 24991833.
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