His-Trp cation-π interaction and its structural role in an α-helical dimer of HIV-1 Vpr protein.

Abstract Vpr is a multifunctional accessory protein of HIV-1 virus and was previously proposed to assume an antiparallel helical dimer with the third helices H III of different subunits facing each other. In this study, we have examined the structure and stability of the antiparallel dimer by using a fragment peptide, Vpr52–80, spanning the H III region. The present analyses of fluorescence, circular dichroism, and UV absorption spectra have shown that a cation–π interaction takes place between protonated His71 and Trp54 located near the opposite ends of the two antiparallel helices. The cation–π interaction induces a small elongation of the H III helix, an increase in thermal stability of the helical dimer, and a modification of the helix arrangement to produce a more compact form. The His71–Trp54 cation–π interaction may be utilized in stabilizing and tuning the dimeric structure of Vpr to achieve proper interactions with other proteins.