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Postgraduate Research : Modulation of Viral Ion Channel Activity
Viral ion channels are encoded by viruses to enhance the efficiency of viral replication by altering electrochemical potentials across host lipid membranes.
They are produced as short monomeric polypeptides and oligomerise within the lipid membrane forming bundles which enable ion flux. Their small size, (approximately one fifth that of mammalian ion channels), means that they can be used to model more complex systems.
The viral ion channel for which the most detailed structural information is available is Vpu, an 81 amino acid integral membrane protein encoded by HIV-1. The transmembrane domain of this protein has been synthesised using continuous-flow solid phase peptide synthesis and the full-length protein has been expressed in recombinant E. coli. Conductance measurements are obtained by bilayer recording of the peptide inserted into artificial black lipid membranes of varying lipid composition.
Bilayer recording and docking simulations are used to study the inhibition of channel activity by HMA (5-(N,N-hexamethylene)amiloride). Novel peptide inhibitors are also under investigation.