Solution Structure and Membrane Interaction of the Cytoplasmic Tail of HIV-1 gp41 Protein

Academic Article

Abstract

  • © 2017 Elsevier Ltd The cytoplasmic tail of gp41 (gp41CT) remains the last HIV-1 domain with an unknown structure. It plays important roles in HIV-1 replication such as mediating envelope (Env) intracellular trafficking and incorporation into assembling virions, mechanisms of which are poorly understood. Here, we present the solution structure of gp41CT in a micellar environment and characterize its interaction with the membrane. We show that the N-terminal 45 residues are unstructured and not associated with the membrane. However, the C-terminal 105 residues form three membrane-bound amphipathic α helices with distinctive structural features such as variable degree of membrane penetration, hydrophobic and basic surfaces, clusters of aromatic residues, and a network of cation-π interactions. This work fills a major gap by providing the structure of the last segment of HIV-1 Env, which will provide insights into the mechanisms of Gag-mediated Env incorporation as well as the overall Env mobility and conformation on the virion surface. Murphy et al. devised new approaches to prepare the HIV-1 gp41CT protein, solved the structure by NMR methods, characterized its interactions with the membrane, and provided a preferred topology of the protein when bound to the membrane.
  • Published In

  • Structure  Journal
  • Digital Object Identifier (doi)

    Author List

  • Murphy RE; Samal AB; Vlach J; Saad JS
  • Start Page

  • 1708
  • End Page

  • 1718.e5
  • Volume

  • 25
  • Issue

  • 11