Conserved Motifs in proteins can be quite beneficial as they may provide insights into the function and structural properties of the protein. In the case of the ORF3a Protein, three conserved motifs were observed:
- Cysteine-rich motif
- SGD motif
- Tyrosine-based motif

Conserved Motifs of the ORF3a Protein

Co-occurring mutations have been observed between ORF3a and the region encoding the (S) spike glycoprotein and this may indicate some form of relation in the functions of the S protein and the ORF3a protein. One major function of the ORF3a protein seems to be in apoptosis (or “programmed cell death”) of host cells which will be discussed in further nodes.

Potential Insights of the Function of the ORF3a protein of SARS-CoV2

Similar to other accessory proteins, ORF3a plays an important role in the virulence of SARS-CoV2 including affecting the host antiviral response. ORF3a codes for a protein that is made of 274 amino acids and three regions: an ion channel, CBM (Caveolin Binding Motif), and TNF Receptor Associated Factor (TRAF). 

Ohio State University, Columbus

Accessory proteins play important roles as virulence factors affecting pathogenicity, release, and stability of SARS-CoV2 and aid in infection, replication, and transmission of the virus between individuals. The SARS-CoV2 accessory proteins are 3a, 3b, p6, 7a, 7b, 8b, 9b, and ORF14.

Accessory Proteins of SARS-CoV2

Hassan, S. S., Choudhury, P. P., Basu, P., & Jana, S. S. (2020). Molecular conservation and Differential mutation on ORF3a gene in Indian SARS-CoV2 genomes. Genomics.

Molecular conservation and Differential mutation on ORF3a gene in Indian
SARS-CoV2 genomes


Ren, Y., Shu, T., Wu, D. et al. The ORF3a protein of SARS-CoV-2 induces apoptosis in cells. Cell Mol Immunol 17, 881–883 (2020). https://doi.org/10.1038/s41423-020-0485-9

The ORF3a protein of SARS-CoV-2 induces apoptosis in cells

In regards to amino acid sequence and composition of proteins, SARS-CoV2 bears many resemblances and similarities with SARS-CoV but there are certainly significant differences as well:
- The 8a accessory protein is absent in SARS-CoV2 but is present in other SARS-CoV.
- The 8b accessory protein’s amino acid sequences is longer in SARS-CoV2 with 121 amino acids compared to the 84 amino acids in other SARS-CoV.
- The 3b accessory protein amino acid sequence is considerably shorter in SARS-CoV2 with just 22 amino acids compared to the 154 amino acids seen in other SARS-CoV.


Amino Acid Differences of Accessory Proteins between Sars-CoV2 and SARS-CoV

The ORF coding the 9b accessory protein is present in the Nucleocapsid gene and is comprised of 98 amino acids. While the function of the 9b accessory protein in SARS-CoV2 is not exactly known, a relative idea of its function can be obtained by understanding its role in SARS-CoV as the 9b sequence is heavily conserved in other SARS isolates (indicating that it probably has a very similar function). the 9b sequence is heavily conserved in other SARS isolates.

9b Accessory Protein of SARS-CoV2

Similar to the ORF 9b protein, the function of the ORF14 accessory protein is not exactly known but it is believed to play a potential role in the interaction between the host cells and the virus. This protein has been seen in SARS-CoV2, SARS-CoV, and SARS-like coronavirus Rp3 (a bat coronavirus). 


ORF14 Accessory Protein of SARS-CoV2

Structure of ORF3a Accessory Protein

Apoptosis, which is essentially cell death that is triggered by certain factors, is an important mechanism in the antiviral immune response as it allows the killing of infected cells which aids in limiting and controlling the infection as well as playing a regulatory role in inflammation. Multiple accessory proteins seem to affect apoptosis of host cells and contribute to viral pathogenesis by doing so, making apoptosis an overlapping and overarching concept regarding accessory protein of SARS-CoV2.

Learn Before

Related

Learn After