Facebook Pixel Code
Banner image
Sharpe Lab

Viroporin structure and function

Viral ion channels

Many RNA viruses encode small integral membrane proteins which are localized primarily within the endoplasmic reticulum and plasma membranes of host cells. These so-called ‘viroporins’ include the HIV-1 Vpu protein, hepatitis C virus (HCV) p7 protein and the coronavirus E (CoVE) protein from the severe acute respiratory syndrome (SARS) virus, and share the characteristic ability to form ion channels or pores.

Through an as-yet uncharacterized mechanism, this activity is essential for viral infectivity in many cases, making viroporins excellent candidates for development of novel antiviral therapies. Thus the details of channel or pore formation by these small (<100 amino acids) proteins, and their effects on membrane stability, are of significant interest.

Despite their biological and medical importance, viroporin structures remain poorly defined. Based on promising results obtained from solid state NMR studies of the structure of the channel-forming protein Vpu from HIV-1, we are using a similar approach to address questions regarding the structural basis for viroporin assembly and cation channel activity in lipid membranes. We are also interested in defining the binding sites for known channel-blocking drugs, as a first step in structure-based drug design targeting viroporins.