Conductance and amantadine binding of a pore formed by a lysine-flanked transmembrane domain of SARS coronavirus envelope protein.
The coronavirus responsible for the severe acute respiratory syndrome (SARS-CoV) contains a small envelope protein, E, with putative involvement in host cell apoptosis and virus morphogenesis. It has been suggested that E protein can form a membrane destabilizing transmembrane (TM) hairpin, or homooligomerize to form a regular TM alpha-helical bundle. We have shown previously that the topology of the alpha-helical putative TM domain of E protein (ETM), flanked by two lysine residues at C and N termini to improve solubility, is consistent with a regular TM alpha-helix, with orientational parameters in lipid bilayers that are consistent with a homopentameric model. Herein, we show that this peptide, reconstituted in lipid bilayers, shows sodium conductance. Channel activity is inhibited by the anti-influenza drug amantadine, which was found to bind our preparation with moderate affinity. Results obtained from single or double mutants indicate that the organization of the transmembrane pore is consistent with our previously reported pentameric alpha-helical bundle model.
Torres
Jaume
J
School of Biological Sciences, Nanyang Technological University, Singapore. jtorres@ntu.edu.sg
Maheswari
Uma
U
Parthasarathy
Krupakar
K
Ng
Lifang
L
Liu
Ding Xiang
DX
Gong
Xiandi
X
D000547:Amantadine / Q000378:metabolism* / Q000494:pharmacology; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D008051:Lipid Bilayers / Q000737:chemistry; D008239:Lysine / Q000737:chemistry*; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000086082:Viroporin Proteins
D000998:Antiviral Agents; C501689:E protein, SARS coronavirus; D008051:Lipid Bilayers; D014759:Viral Envelope Proteins; D000086082:Viroporin Proteins; D000547:Amantadine; D008239:Lysine