5bz0

Structural highlights

Function

[R1AB_IBVB] The replicase polyprotein of coronaviruses is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.^[1] The papain-like proteinase (PL-PRO) is responsible for the cleavages located at the N-terminus of replicase polyprotein. Activity of PL-PRO is dependent on zinc (By similarity).^[2] The main proteinase 3CL-PRO is responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK (By similarity).^[3] The peptide p16 might be involved in the EGF signaling pathway.^[4] The helicase which contains a zinc finger structure displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. Its ATPase activity is strongly stimulated by poly(U), poly(dT), poly(C), poly(dA), but not by poly(G) (By similarity).^[5] The exoribonuclease acts on both ssRNA and dsRNA in a 3' to 5' direction (By similarity).^[6] Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter (By similarity).^[7] Nsp9 is a ssRNA-binding protein (By similarity).^[8] NendoU is a Mn(2+)-dependent, uridylate-specific enzyme, which leaves 2'-3'-cyclic phosphates 5' to the cleaved bond (By similarity).^[9] [RS27A_BOVIN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity). Ribosomal protein S27a is a component of the 40S subunit of the ribosome.

References

1. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001
2. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001
3. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001
4. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001
5. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001
6. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001
7. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001
8. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001
9. ↑ Liu C, Xu HY, Liu DX. Induction of caspase-dependent apoptosis in cultured cells by the avian coronavirus infectious bronchitis virus. J Virol. 2001 Jul;75(14):6402-9. PMID:11413307 doi:http://dx.doi.org/10.1128/JVI.75.14.6402-6409.2001