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 N protein from Human SARS CoV has one phosphorylation site (residue S 177 ) and several regions with compositional biases, such as Ser-rich (residues 181-213), Poly-Leu, Poly-Gln, and Ploy-Lys (residues 220-225, 240-245, and 370-376), all predicted to be disordered. Similarly, in N protein from Bat CoV, S 176 is phosphorylated, and this protein has Ser-rich, Poly-Leu, and Ploy-Lys regions (residues 176-206, 219-224, and 369-375, respectively), all of which are disordered. It has been reported to interact using the central disordered region with M protein, hnRNP A1, and self N-N interaction [82] [83] [84] . The middle flexible region is also responsible for its RNA-binding activity [85] . Deletion of 184-196 residues, 169-308 residues, 161-210 residues of N abolishes its multimerization, RNAbinding capacity, and hnRNP A1 interactions respectively. Supplementary Table 7 and 8, and Table 2 shows that N protein is heavily decorated with numerous MoRFs, suggesting that this protein is a promiscuous binder. Long disorder-based protein bonding regions at Nand C-terminus of N protein of all three viruses were observed by all four predictors (MoRFchibi_web, ANCHOR, MoRFPred, and DISOPRED3). Indeed, this is the single protein where we found many MoRFs as compared with the other structural, non-structural and accessory proteins of CoVs. The MoRFs present in these regions may mediate the abovementioned interactions of N proteins. Figure 6A2 represents another important disorderrelated functional feature of the N protein. In fact, the CTD homodimer shown there is characterized by highly intertwined morphology, which is typically a result of bindinginduced folding [86] [87] [88] , indicating that a very significant part of CTD gains structure during dimerization. We identified numerous RNA binding residues in all three viruses using PPRint server. This finding supports the function of N protein as it interacts with genomic RNA for a ribonucleoprotein core formation which is crucial step for RNA encapsidation during viral particle assembly. In addition, DRNApred and DisoRDPbind predicts multiple DNA binding residues for N protein in SARS-CoV-2, Human SARS, and Bat CoV. The long flexible (IDPRs) regions at N and C-terminus of SARS-CoV-2 have long protein-binding as well as nucleotide-binding regions that may have important role in its interaction with viral RNA. author/funder. All rights reserved. No reuse allowed without permission.