Abstract
AbstractThe SARS-CoV-2 E protein is a transmembrane (TM) protein with its N-terminus exposed on the external surface of the virus. At debate is its oligomeric state, let alone its function. Here, the TM structure of the E protein is characterized by oriented sample and magic angle spinning solid-state NMR in lipid bilayers and refined by molecular dynamics simulations. This protein was previously found to be a pentamer, with a hydrophobic pore that appears to function as an ion channel. We identify only a front-to-front, symmetric helix-helix interface, leading to a dimeric structure that does not support channel activity. The two helices have a tilt angle of only 6°, resulting in an extended interface dominated by Leu and Val sidechains. While residues Val14-Thr35 are almost all buried in the hydrophobic region of the membrane, Asn15 lines a water-filled pocket that potentially serves as a drug-binding site. The E and other viral proteins may adopt different oligomeric states to help perform multiple functions.
Funder
U.S. Department of Health & Human Services | National Institutes of Health
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference60 articles.
1. World Health Organization https://www.who.int/emergencies/diseases/novel-coronavirus-2019 (2023).
2. Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020).
3. Aronin, S. I. & Sadigh, M. Severe acute respiratory syndrome. Conn. Med. 68, 207–215 (2004).
4. de Groot, R. J. et al. Commentary: Middle East Respiratory Syndrome Coronavirus (MERS-CoV): announcement of the coronavirus study group. J. Virol. 87, 7790–7792 (2013).
5. Wilson, L., McKinlay, C., Gage, P. & Ewart, G. SARS coronavirus E protein forms cation-selective ion channels. Virology 330, 322–331 (2004).
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