Structure-function correlates of Vpu, a membrane protein of HIV-1.
Vpu, a membrane protein from human immunodeficiency virus-1, folds into two distinct structural domains with different biological activities: a transmembrane (TM) helical domain involved in the budding of new virions from infected cells, and a cytoplasmic domain encompassing two amphipathic helices, which is implicated in CD4 degradation. The molecular mechanism by which Vpu facilitates virion budding is not clear. This activity of Vpu requires an intact TM helical domain. And it is known that oligomerization of the VPU TM domain results in the formation of sequence-specific, cation-selective channels. It has been shown that the channel activity of Vpu is confined to the TM domain, and that the cytoplasmic helices regulate the lifetime of the Vpu channel in the conductive state. Structure-function correlates based on the convergence of information about the channel activity of Vpu reconstituted in lipid bilayers and on its 3-D structure in membranes by a combination of solution and solid-state nuclear magnetic resonance spectroscopy may provide valuable insights to understand the role of Vpu in the pathogenesis of AIDS and for drug design aimed to block channel activity.
Montal
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Section of Neurobiology, Division of Biological Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0366, USA. mmontal@ucsd.edu
D000163:Acquired Immunodeficiency Syndrome; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000096:biosynthesis; D002412:Cations; D003593:Cytoplasm / Q000378:metabolism; D054298:Human Immunodeficiency Virus Proteins; D007477:Ions; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000502:physiology*; D014771:Virion; D000086082:Viroporin Proteins
D015704:CD4 Antigens; D002412:Cations; D054298:Human Immunodeficiency Virus Proteins; D007477:Ions; D008051:Lipid Bilayers; D011994:Recombinant Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins