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

Montal, Mauricio³  Oblatt-Montal, Myrta³  Schubert, Ulrich¹  Ferrer-Montiel, Antonio V.³  Henklein, Peter²  Strebel, Klaus¹ 

[1] Laboratory 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;Institut für Biochemie, Universitätsklinik (Charité), Humboldt-Universität zu Berlin, Germany;Department of Biology, University of California San Diego, La Jolla, CA 92093-0366, USA

关键词: Channel protein;    Lipid bilayer;    Transmembrane helix;    AIDS;    Reconstitution;   

DOI  :  10.1016/S0014-5793(96)01146-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown