title: C-terminal hydrophobic region in human bone marrow stromal cell antigen 2 (BST-2)/tetherin protein functions as second transmembrane motif.
abstract: BST-2/CD317/HM1.24/tetherin is a host factor that inhibits the release of HIV-1 and other enveloped viruses. Structurally, tetherin consists of an N-terminal transmembrane (TM) region, a central coiled coil motif, and a putative C-terminal glycosylphosphatidylinositol (GPI) anchor motif. A current working model proposes that BST-2 inhibits virus release by physically tethering viral particles to the cell surface via its TM motif and GPI anchor. Here we analyzed the functional importance of the C-terminal GPI anchor motif in BST-2. We replaced the GPI anchor motif in BST-2 with the TM regions of several surface markers and found that the TM motifs of CD40 and transferrin receptor, but not that of CD45, could functionally substitute for a GPI anchor in BST-2. Conversely, replacing the TM region of CD4 by the putative GPI anchor signal of human BST-2 resulted in proper membrane targeting and surface expression of the chimeric protein, indicating that the BST-2 GPI anchor signal can function as a bona fide TM region. In fact, attempts to demonstrate GPI anchor modification of human BST-2 by biochemical methods failed. Our results demonstrate that the putative C-terminal GPI anchor motif in human BST-2 fulfills the requirements of a bona fide TM motif, leading us to propose that human BST-2 may in fact contain a second TM segment rather than a GPI anchor.
authors.affiliation: Laboratory of Molecular Microbiology, Viral Biochemistry Section, NIAID, National Institutes of Health, Bethesda, Maryland 20892-0460, USA.
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Andrew
authors.forename: Sandra
authors.initials: S
authors.lastname: Kao
authors.forename: Klaus
authors.initials: K
authors.lastname: Strebel
mesh_terms: D020816:Amino Acid Motifs; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D000074010:Bone Marrow Stromal Antigen 2
chemical_list: D015703:Antigens, CD; D019013:CD40 Antigens; D058851:GPI-Linked Proteins; D017261:Glycosylphosphatidylinositols; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; C094572:BST2 protein, human; D000074010:Bone Marrow Stromal Antigen 2