Novel Immunoglobulin Domain Proteins Provide Insights into Evolution and Pathogenesis Mechanisms of SARS-Related Coronaviruses

Yongjun Tan; Theresa Schneider; Matthew Leong; L Aravind; Dapeng Zhang

The homology model of ORF8, based on the structure of SARS-CoV ORF7a (pdb id:1XAK), suggests that 161 this insert augments a potential peptide-ligand binding groove that has been proposed for ORF7a 162 ( Figure 2B and Figure S3 ). Hence, the emergence of the insert has gone hand-in-hand with the 163 acquisition of a modified interaction interface. 164 165 Besides these families, we identified a fourth family of Ig domains from the same Alpha-CoVs which 166 contain the above-discussed ORF7a/8-like Ig family ( Figure 3A ). These Alpha-CoVs typically possess one 167 or two paralogous copies annotated as either ORF4a/b or NS5a/b. From their sequences, these Ig 168 domains are not closely related to the ORF7a and ORF8 Ig domains ( Figure S4 ). However, profile-profile 169 searches have shown that they are related to Ig domains found in the adenoviral E3-CR1 proteins 170 (probability: 90% of matching the Pfam CR1 Ig domain profile) ( Figure S4 ). In these searches, they also 171 yield weaker hits to two other Ig domains, namely the poxviral decoy interferon receptors and human T-172 cell surface CD3 zeta ( Figure S4 ). 173