Comformational analysis by NMR and molecular modelling of the 41-62 hydrophilic region of HIV-1 encoded virus protein U (Vpu). Effect of the phosphorylation on sites 52 and 56

摘要

The peptide of 22 amino acid residues, Vpu_P~(41-62), phosphorylated at the two sites Ser~52 and Ser~56 has been implicated in the degradation of CD4 receptor molecules, an important stage of the pathways to human immunodeficiency virus type 1 pathology (HIV-1). In order to assess the structural influence of phosphorylation, a conformational analysis by NMR and molecular simulation have been carried out for the phosphorylated Vpu_P~(41-62), and non-phosphorylated Vpu~(41-62) in both H_2O (at pH 3.5 and 7.2) and a 1:1 mixture of H_2O and trifluoroethanol. Analysis of the short-, medium-range NOE connectivities and of the secondary chemical shifts indicated that the peptide segment (42-49) shows a less well-defined helix propensity. The 50-62 segment forms a loop with the phosphate group pointing away, a short #beta#-strand and a flexible extended 'tail' of residues 60-62 segment forms a loop with the phosphate group pointing away, a short #beta#-strand and a flexible extended 'tail' of residues 60-62. Differences in this molecular region 50-62 suggest that conformational changes of Vpu_P, play a potential role in Vpu_P-induced degradation of CD4 molecules.