Dark Proteome of Newly Emerged SARS-CoV-2 in Comparison with Human and Bat Coronaviruses

Rajanish Giri; Taniya Bhardwaj; Meenakshi Shegane; Bhuvaneshwari R. Gehi; Prateek Kumar; Kundlik Gadhave

The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.13.990598 doi: bioRxiv preprint RANTES [109, 110] . In another study, overexpression of BCL-XL in 293T cells blocked the ORF7a mediated apoptosis [111] . On the other hand, ORF7b is an integral membrane protein that has been shown to localize in the Golgi complex [112, 113] . The same reports also confirm the role of ORF7b as an accessory as well as a structural protein in SARS-CoV virion [112, 113] . Figure 10D represents the 1.8 Ã… X-ray crystal structure of the 14-96 fragment of the ORF7a from Human SARS CoV (PDB ID: 1XAK) and demonstrates the compact seven-stranded topology of this protein, which is similar to that of the Ig-superfamily members [114] . Importantly, in this crystal structure, residues 82-96 constituted the region with missing electron density, indicating high structural flexibility of this segment. In line with this hypothesis, the NMR solution structure of the 16-99 fragment of the ORF7a from Human SARS CoV (PDB ID: 1YO4) showed that residues 81-99 are highly disordered [115] . At the domain level, the structure of the ORF7a protein includes a signal peptide, a luminal domain, a transmembrane domain, and a short cytoplasmic tail at the C-terminus [95, 114] . We found that 121-residue-long ORF7a protein of SARS-CoV-2 shares 89.26% and 85.95% sequence identity with ORF7a proteins of Bat CoV and Human SARS CoV, respectively ( Figure 10E) . On the other hand, the ORF7b of SARS-CoV-2 is found to be closer to ORF7b author/funder. All rights reserved. No reuse allowed without permission.