Biophysical characterization of Vpu from HIV-1 suggests a channel-pore dualism

Vpu from HIV-1 is an 81 amino acid type I integral membrane protein which consists of a cytoplasmic and a transmembrane (TM) domain. The TM domain is known to alter membrane permeability for ions and substrates when inserted into artificial membranes. Peptides corresponding to the TM domain of Vpu (Vpu _1-32) and mutant peptides (Vpu_1-32-W23L, Vpu _1-32-R31V, Vpu_1-32-S24L) have been synthesized and reconstituted into artificial lipid bilayers. All peptides show channel activity with a main conductance level of around 20 pS. Vpu_1-32-W23L has a considerable flickering pattern in the recordings and longer open times than Vpu_1-32. Whilst recordings for Vpu_1-32-R31V are almost indistinguishable from those of the WT peptide, recordings for Vpu _1-32-S24L do not exhibit any noticeable channel activity. Recordings of WT peptide and Vpu_1-32-W23L indicate Michaelis-Menten behavior when the salt concentration is increased. Both peptide channels follow the Eisenman series I, indicative for a weak ion channel with almost pore like characteristics.