Structural highlights
Publication Abstract from PubMedBST-2/tetherin is a host anti-viral molecule that functions to potently inhibit the release of enveloped viruses from infected cells. In return, viruses have evolved antagonists to this activity. BST-2 traps budding virions by using two separate membrane-anchoring regions that simultaneously incorporate into the host and viral membrane. Here we detail the structural and biophysical properties of the full BST-2 ectodomain, which spans the two membrane anchors. The 1.6 Angstrom crystal structure of the complete mouse BST-2 ectodomain reveals a ~145 Angstrom parallel dimer in an extended alpha-helix conformation that predominantly forms a coiled-coil bridged by three intermolecular disulfides that are required for stability. Sequence analysis in the context of the structure reveals an evolutionarily conserved design that destabilizes the coiled-coil, resulting in a labile superstructure, as evidenced by solution X-ray scattering displaying bent conformations spanning 150 Angstrom and 180 Angstrom for mouse and human BST-2 ectodomains, respectively. Additionally, crystal packing analysis reveals possible curvature-sensing tetrameric structures that may aid in proper placement of BST-2 during the genesis of viral progeny. Overall, this extended coiled-coil structure with inherent plasticity is undoubtedly necessary to accommodate the dynamics of virus budding while ensuring separation of the anchors. Structural and biophysical analysis of BST-2/tetherin ectodomains reveal an evolutionary conserved design to inhibit virus release.,Swiecki M, Scheaffer SM, Allaire M, Fremont DH, Colonna M, Brett TJ J Biol Chem. 2010 Nov 17. PMID:21084286[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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