Identification of an ion channel activity of the Vpu transmembrane domain and its involvement in the regulation of virus release from HIV‐1‐infected cells

FEBS Letters - Tập 398 Số 1 - Trang 12-18 - 1996
Ulrich S. Schubert1, Antonio Ferrer‐Montiel2, M. Oblatt-Montal2, Peter Henklein3, Klaus Strebel1, M Montal2
1Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, Room 312, 9000 Rockville Pike, Bethesda, MD 20892-0460, USA
2Department of Biology, University of California San Diego, La Jolla, CA 92093-0366, USA
3Institut für Biochemie, Universitätsklinik (Charité), Humboldt-Universität zu Berlin, Germany

Tóm tắt

HIV‐1 Vpu catalyzes two independent functions, degradation of the virus receptor CD4 in the endoplasmic reticulum and enhancement of virus release from the cell surface. These activities are confined to distinct structural domains of Vpu, the cytoplasmic tail and the transmembrane (TM) anchor, respectively. It was recently reported that Vpu forms cationselective ion channels in lipid bilayers. Here we report that this property of Vpu is a characteristic of its TM anchor. Expression of full‐length Vpu in Xenopus oocytes increases membrane conductance. The Vpu‐induced conductance is selective to monovalent cations over anions, does not discriminate Na+ over K+ and shows marginal permeability to divalent cations. Notably, introduction of the scrambled TM sequence into full‐length Vpu abrogates its capacity to increase membrane conductance in oocytes and to promote virus release from infected cells. Reconstitution of synthetic Vpu fragments in lipid bilayers identified an ion channel activity for a sequence corresponding to the TM domain of Vpu. In contrast, a peptide with the same amino acid composition but with a scrambled sequence does not form ion channels. Our findings therefore suggest that the ability of Vpu to increase virus release from infected cells may be correlated with an ion channel activity of the TM domain, thereby providing a potential target for drug intervention based on the development of Vpu‐specific channel blockers.

Từ khóa


Tài liệu tham khảo

10.1126/science.3261888

10.1038/334532a0

10.1128/jvi.63.9.3784-3791.1989

10.1128/jvi.67.8.5056-5061.1993

10.1128/jvi.66.12.7193-7200.1992

10.1128/jvi.69.12.7699-7711.1995

10.1128/jvi.68.4.2260-2271.1994

10.1128/jvi.70.2.809-819.1996

10.1128/jvi.67.7.3877-3884.1993

10.1128/jvi.69.3.1510-1520.1995

10.1006/jmbi.1994.1114

10.1111/j.1432-1033.1992.tb16707.x

10.1128/jvi.70.10.7108-7115.1996

Schubert U., 1995, AIDS Res. Hum. Retrov., 11, S 114

10.1128/JVI.59.2.284-291.1986

10.1038/313277a0

10.1006/meth.1994.1008

1972 M. Montal P. Mueller Proc. Natl. Acad. Sci. USA 3562 3566

10.1007/978-1-4757-1361-9_8

10.1085/jgp.83.4.473

1990 S. Oiki V. Madison M. Montal Proteins Struct. Funct. Genet. 226 236

D. Colquhoun 1971 Clarendon Press Oxford

White M.M., 1990, Mol. Pharmacol., 37, 720

10.1016/0092-8674(92)90452-I

10.1016/S0006-3495(95)80052-4

10.1016/S0006-3495(95)79964-7

10.1146/annurev.bb.24.060195.000335

10.1126/science.1321498

1989 A.L. Burns K. Magendzo A. Shirvan M. Srivastava E. Rojas M.R. Alijani H.B. Pollard Proc. Natl. Acad. Sci. USA 3798 3802

10.1016/0042-6822(91)90115-R

10.1016/0042-6822(91)90075-M

10.1111/j.1399-3011.1995.tb01565.x

10.1016/0042-6822(92)91187-Y

10.1016/0042-6822(92)90730-D

10.1128/jvi.66.8.5119-5126.1992

10.1128/JVI.64.2.621-629.1990

10.1111/j.1399-3011.1996.tb01359.x

Thông tin
Thông tin xuất bản

FEBS Letters

Tập 398 Số 1

12-18

Thông tin tác giả