The structure of the HIV-1 Vpu ion channel: Modelling and simulation studies

F. S. Cordes, A. Kukol, L. R. Forrest, I. T. Arkin, M. S.P. Sansom, W. B. Fischer*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Vpu is an 81 amino acid auxiliary protein in HIV-1 which exhibits channel activity. We used two homo-pentameric bundles with the helical transmembrane segments derived from FTIR spectroscopy in combination with a global molecular dynamics search protocol: (i) tryptophans (W) pointing into the pore, and (ii) W facing the lipids. Two equivalent bundles have been generated using a simulated annealing via a restrained molecular dynamics simulations (SA/MD) protocol. A fifth model was generated via SA/MD with all serines facing the pore. The latter model adopts a very stable structure during the 2 ns of simulation. The stability of the models with W facing the pore depends on the starting structure. A possible gating mechanism is outlined.

Original languageAmerican English
Pages (from-to)291-298
Number of pages8
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1512
Issue number2
DOIs
StatePublished - 6 Jun 2001
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported with a grant to M.S.P.S. from the Wellcome Trust. F.S.C. thanks the Deutsche Volk Stiftung for a stipend. This work was supported by the EC with a TMR-Research Fellowship for W.B.F. We acknowledge the Oxford Super Computer facility for providing us with computer time.

Keywords

  • Gating
  • HIV-1
  • Molecular dynamics
  • Viral ion channel
  • Vpu

Fingerprint

Dive into the research topics of 'The structure of the HIV-1 Vpu ion channel: Modelling and simulation studies'. Together they form a unique fingerprint.

Cite this