This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sramala, I. Articles by Fischer, W. B. Search for Related Content PubMed PubMed Citation Articles by Sramala, I. Articles by Fischer, W. B.

Molecular Dynamics Simulations on the First Two Helices of Vpu from HIV-1

I. Sramala ^*, V. Lemaitre ^* , J. D. Faraldo-Gómez , S. Vincent , A. Watts ^* and W. B. Fischer ^*

^* Biomembrane Structure Unit, Department of Biochemistry, Oxford University, Oxford OX1 3QU, UK; Nestlé Research Center, Bioscience Department, Vers-Chez-Les-Blanc, CH-1000 Lausanne 26, Switzerland; and Laboratory of Molecular Biophysics, Department of Biochemistry, Oxford University, Oxford OX1 3QU, UK

Correspondence: Address reprint requests to W. B. Fischer, Tel.: +44-1865-275776; Fax: +44-1865-275234; E-mail: wolfgang.fischer{at}bioch.ox.ac.uk.

Vpu is an 81 amino acid protein of HIV-1 with two phosphorylation sites. It consists of a short N-terminal end traversing the bilayer and a longer cytoplasmic part. The dual functional role of Vpu is attributed to these topological distinct regions of the protein. The first 52 amino acids of Vpu (HV1H2) have been simulated, which are thought to be embedded in a fully hydrated lipid bilayer and to consist of a transmembrane helix (helix-1) connected via a flexible linker region, including a Glu-Tyr-Arg (EYR) motif, with a second helix (helix-2) residing with its helix long axis on the bilayer surface. Repeated molecular dynamics simulations show that Glu-28 is involved in salt bridge formation with Lys-31 and Arg-34 establishing a kink between the two helices. Helix-2 remains in a helical conformation indicating its stability and function as a "peptide float," separating helix-1 from the rest of the protein. This leads to the conclusion that Vpu consists of three functional modules: helix-1, helix-2, and the remaining residues toward the C-terminal end.