Vpu (virus protein _u_) from HIV-1 is a membrane protein that accelerates the release of virus particles from infected cells and the degradation of CD4 receptor proteins. This small 81 residue protein appears to have one hydrophobic and two amphipathic helices as well as two phosphorylation sites, which are presumed to be involved in its regulation. The protein may act as a channel in bilayers, and as such, provides a target for structure based drug design. In these collaborative studies with U. Schubert and K. Strebel of the NIH, initial results have been obtained on uniformly 15N labeled vpu in both oriented and unoriented lipid bilayers. The unoriented spectrum has isotropic resonance intensity from mobile backbone sites superimposed on a powder pattern from the rigidly held backbone sites. This is fully consistent with the protein having mobile terminal regions and mobile loops connecting the helices. Experiments were also performed on oriented samples in order to find the organization of the helices in the membrane. These are at an early stage, but show clear evidence of the existence of both trans-membrane and in-plane helices. Studies in progess involve the comparison of phosphorylated and unphosphorylated protein and the resolution of resonances from specific sites through selective isotopic labeling and multidimensional solid-state NMR experiments.
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