Structure
Volume 25, Issue 11, 7 November 2017, Pages 1708-1718.e5
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Article
Solution Structure and Membrane Interaction of the Cytoplasmic Tail of HIV-1 gp41 Protein

https://doi.org/10.1016/j.str.2017.09.010Get rights and content
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Highlights

  • Devised new approaches to generate HIV-1 gp41CT protein via recombinant techniques

  • Determined the NMR structure of gp41CT in micellar solution

  • Characterized gp41CT interaction with the membrane

  • Provided a preferred topology of gp41CT bound to the membrane

Summary

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.

Keywords

HIV-1
envelope protein
cytoplasmic tail
gp41
NMR
membrane
micelles
bicelles
Gag polyprotein
matrix protein

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2

These authors contributed equally

3

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