Detailed Structural Analyses of the Human Immunodeficiency Virus gp41 Glycoprotein Transmembrane Domain Reveal New Potential Targets for Vaccines and Viral Inhibitors^♦

The Atomic Structure of the HIV-1 gp41 Transmembrane Domain and Its Connection to the Immunogenic Membrane-proximal External Region

♦ See referenced article, J. Biol. Chem. 2015, 290, 12999–13015

The human immunodeficiency virus, or HIV, relies on two glycoproteins, gp41 and gp120, that form a non-covalent complex as the viral envelope. However, structural details of a transmembrane anchor found in gp41 are not known. In this Paper of the Week, a team led by José Nieva at the University of the Basque Country in Spain, M. Ángeles Jiménez at the Institute of Physical Chemistry “Rocasolano” (IQFR-CSIC) in Spain, and Jose M. M. Caaveiro at the University of Tokyo carried out high-resolution nuclear magnetic resonance spectroscopy to analyze the anchor. They discovered that the anchor contains two helices that are held together by a flexible region. Further biophysical analyses revealed that the N-terminal helix was a scaffold for neutralizing antibodies. The C-terminal helix acted as an immunosuppressor and may contribute to the late stages of the viral fusion process into the host cell. The investigators concluded, “These data may guide the rational design of vaccines and inhibitors.”