Structural similarity between the p17 matrix protein of HIV-1 and interferon-γ

THE human immunodeficiency virus (HIV) matrix protein, p17, forms the outer shell of the core of the virus, lining the inner surface of the viral membrane1–4. The protein has several key functions. It orchestrates viral assembly via targeting signals that direct the gag precursor polyprotein, p55, to the host cell membrane1,5–7 and it interacts with the transmembrane protein, gp41, to retain the env-encoded proteins in the virus8. In addition, pi7 contains a nuclear localization signal that directs the preintegration complex to the nucleus of infected cells9. This permits the virus to infect productively non-dividing cells, a distinguishing feature of HIV and other lentiviruses. We have determined the solution structure of p17 by nuclear magnetic resonance (NMR) with a root-mean square deviation for the backbone of the well-defined regions of 0.9 A. It consists of four helices connected by short loops and an irregular, mixed β-sheet which provides a positively charged surface for interaction with the inner layer of the membrane. The helical topology is unusual; the Brookhaven protein database contains only one similar structure, that of the immune modulator interferon-γ.