5xer

From Proteopedia

TK9 NMR structure in DPC micelle

Structural highlights

5xer is a 1 chain structure with sequence from Severe acute respiratory syndrome-related coronavirus. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

VEMP_SARS Plays a central role in virus morphogenesis and assembly. Acts as a viroporin and self-assembles in host membranes forming pentameric protein-lipid pores that allow ion transport. Also plays a role in the induction of apoptosis (By similarity). Activates the host NLRP3 inflammasome, leading to IL-1beta overproduction.[HAMAP-Rule:MF_04204]^[1] ^[2]

Publication Abstract from PubMed

In recent years, several studies based on the interaction of self-assembling short peptides derived from viroporins with model membranes, have improved our understanding of the molecular mechanism of corona virus (CoV) infection under physiological conditions. In this study, we have characterized the mechanism of membrane interaction of a short, 9-residue peptide TK9 (T(55)VYVYSRVK(63)) that had been derived from the carboxyl terminal of the Severe Acute Respiratory Syndrome (SARS) corona virus (SARS CoV) envelope (E) protein. The peptide has been studied for its physical changes in the presence of both zwitterionic DPC and negatively charged SDS model membrane micelles, respectively, with the help of a battery of biophysical techniques including two-dimensional solution state NMR spectroscopy. Interestingly, in both micellar environments, TK9 adopted an alpha helical conformation; however, the helical propensities were much higher in the case of DPC compared to those of SDS micelle, suggesting that TK9 has more specificity towards eukaryotic cell membrane than the bacterial cell membrane. The orientation of the peptide TK9 also varies in the different micellar environments. The peptide's affinity was further manifested by its pronounced membrane disruption ability towards the mammalian compared to the bacterial membrane mimic. Collectively, the in-depth structural information on the interaction of TK9 with different membrane environments explains the host specificity and membrane orientation owing to subsequent membrane disruption implicated in the viral pathogenesis.

Structural insights of a self-assembling 9-residue peptide from the C-terminal tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high and low resolution spectroscopic study.,Ghosh A, Bhattacharyya D, Bhunia A Biochim Biophys Acta Biomembr. 2018 Feb;1860(2):335-346. doi:, 10.1016/j.bbamem.2017.10.015. Epub 2017 Oct 14. PMID:29038024^[3]

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

References

↑ Nieto-Torres JL, DeDiego ML, Verdiá-Báguena C, Jimenez-Guardeño JM, Regla-Nava JA, Fernandez-Delgado R, Castaño-Rodriguez C, Alcaraz A, Torres J, Aguilella VM, Enjuanes L. Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis. PLoS Pathog. 2014 May 1;10(5):e1004077. PMID:24788150 doi:10.1371/journal.ppat.1004077
↑ Nieto-Torres JL, Verdiá-Báguena C, Jimenez-Guardeño JM, Regla-Nava JA, Castaño-Rodriguez C, Fernandez-Delgado R, Torres J, Aguilella VM, Enjuanes L. Severe acute respiratory syndrome coronavirus E protein transports calcium ions and activates the NLRP3 inflammasome. Virology. 2015 Nov;485:330-9. PMID:26331680 doi:10.1016/j.virol.2015.08.010
↑ Ghosh A, Bhattacharyya D, Bhunia A. Structural insights of a self-assembling 9-residue peptide from the C-terminal tail of the SARS corona virus E-protein in DPC and SDS micelles: A combined high and low resolution spectroscopic study. Biochim Biophys Acta Biomembr. 2018 Feb;1860(2):335-346. doi:, 10.1016/j.bbamem.2017.10.015. Epub 2017 Oct 14. PMID:29038024 doi:http://dx.doi.org/10.1016/j.bbamem.2017.10.015