Bundles Consisting of Extended Transmembrane Segments of Vpu from HIV-1: Computer Simulations and Conductance Measurements
Part of the genome of the human immunodeficiency virus type 1 (HIV-1) encodes for a short membrane protein Vpu, which has a length of 81 amino acids. It has two functional roles: (i) to downregulate CD4 and (ii) to support particle release. These roles are attributed to two distinct domains of the...
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Published in | Biochemistry (Easton) Vol. 41; no. 23; pp. 7359 - 7365 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Chemical Society
11.06.2002
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Subjects | |
Online Access | Get full text |
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Summary: | Part of the genome of the human immunodeficiency virus type 1 (HIV-1) encodes for a short membrane protein Vpu, which has a length of 81 amino acids. It has two functional roles: (i) to downregulate CD4 and (ii) to support particle release. These roles are attributed to two distinct domains of the peptide, the cytoplasmic and transmembrane (TM) domains, respectively. It has been suggested that the enhanced particle release function is linked to the ion channel activity of Vpu, with a slight preference for cations over anions. To allow ion flux across the membrane Vpu would be required to assemble in homooligomers to form functional water-filled pores. In this study molecular dynamics simulations are used to address the role of particular amino acids in 4, 5, and 6 TM helix bundle structures. The helices (Vpu6 - 33) are extended to include hydrophilic residues such as Glu, Tyr, and Arg (EYR motif). Our simulations indicate that this motif destabilizes the bundles at their C-terminal ends. The arginines point into the pore to form a positive charged ring that could act as a putative selectivity filter. The helices of the bundles adopt slightly higher average tilt angles with decreasing number of helices. We also suggest that the helices are kinked. Conductance measurements on a peptide (Vpu1 - 32) reconstituted into lipid membranes show that the peptide forms ion channels with several conductance levels. |
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Bibliography: | ark:/67375/TPS-J9J1BZ26-5 W.B.F. thanks the EC for a TMR research fellowship. F.S.C. was supported by the Deutsche Volk Stiftung. A.W. thanks the BBSRC for a BBSRC Research Fellowship grant. istex:2B26091B07C1F3C068437CD2EE8462DC075EFF8B ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0006-2960 1520-4995 |
DOI: | 10.1021/bi025518p |