5k6k

From Proteopedia

Zika virus non-structural protein 1 (NS1)

Structural highlights

5k6k is a 2 chain structure with sequence from Zika virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.89Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

POLG_ZIKV Protein C: Encapsulates the genomic RNA.[UniProtKB:P17763] prM: Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated.[UniProtKB:P17763] Envelope protein E: Binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes.[UniProtKB:P17763] Non-structural protein 1: Involved in virus replication and regulation of the innate immune response.[UniProtKB:P17763] Non-structural protein 2A: May be involved viral RNA replication and capsid assembly.[UniProtKB:P09732] Non-structural protein 4A: Induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the helicase region of Serine protease NS3 chain.[UniProtKB:P17763] Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[UniProtKB:P17763] Non-structural protein 4B: Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway.[UniProtKB:P17763]

Publication Abstract from PubMed

The Zika virus, which has been implicated in an increase in neonatal microcephaly and Guillain-Barre syndrome, has spread rapidly through tropical regions of the world. The virulence protein NS1 functions in genome replication and host immune-system modulation. Here, we report the crystal structure of full-length Zika virus NS1, revealing an elongated hydrophobic surface for membrane association and a polar surface that varies substantially among flaviviruses.

Extended surface for membrane association in Zika virus NS1 structure.,Brown WC, Akey DL, Konwerski JR, Tarrasch JT, Skiniotis G, Kuhn RJ, Smith JL Nat Struct Mol Biol. 2016 Jul 25. doi: 10.1038/nsmb.3268. PMID:27455458^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Brown WC, Akey DL, Konwerski JR, Tarrasch JT, Skiniotis G, Kuhn RJ, Smith JL. Extended surface for membrane association in Zika virus NS1 structure. Nat Struct Mol Biol. 2016 Jul 25. doi: 10.1038/nsmb.3268. PMID:27455458 doi:http://dx.doi.org/10.1038/nsmb.3268