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Structure of Tupaia Paramyxovirus C protein
Structural highlights
FunctionPublication Abstract from PubMedThe protein C is a small viral protein encoded in an overlapping frame of the P gene in the subfamily Orthoparamyxovirinae. This protein, expressed by alternative translation initiation, is a virulence factor that regulates viral transcription, replication, and production of defective interfering RNA, interferes with the host-cell innate immunity systems and supports the assembly of viral particles and budding. We expressed and purified full-length and an N-terminally truncated C protein from Tupaia paramyxovirus (TupV) C protein (genus Narmovirus). We solved the crystal structure of the C-terminal part of TupV C protein at a resolution of 2.4 A and found that it is structurally similar to Sendai virus C protein, suggesting that despite undetectable sequence conservation, these proteins are homologous. We characterized both truncated and full-length proteins by SEC-MALLS and SEC-SAXS and described their solution structures by ensemble models. We established a mini-replicon assay for the related Nipah virus (NiV) and showed that TupV C inhibited the expression of NiV minigenome in a concentration-dependent manner as efficiently as the NiV C protein. A previous study found that the Orthoparamyxovirinae C proteins form two clusters without detectable sequence similarity, raising the question of whether they were homologous or instead had originated independently. Since TupV C and SeV C are representatives of these two clusters, our discovery that they have a similar structure indicates that all Orthoparamyxovirine C proteins are homologous. Our results also imply that, strikingly, a STAT1-binding site is encoded by exactly the same RNA region of the P/C gene across Paramyxovirinae, but in different reading frames (P or C), depending on which cluster they belong to. Orthoparamyxovirinae C Proteins Have a Common Origin and a Common Structural Organization.,Roy A, Chan Mine E, Gaifas L, Leyrat C, Volchkova VA, Baudin F, Martinez-Gil L, Volchkov VE, Karlin DG, Bourhis JM, Jamin M Biomolecules. 2023 Mar 1;13(3):455. doi: 10.3390/biom13030455. PMID:36979390[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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