Summary for 3NWH
| Entry DOI | 10.2210/pdb3nwh/pdb |
| Related | 2XG7 |
| Descriptor | Bone marrow stromal antigen 2 (2 entities in total) |
| Functional Keywords | coiled-coil, innate immunity, antiviral protein |
| Biological source | Homo sapiens (human) |
| Cellular location | Golgi apparatus, trans-Golgi network: Q10589 |
| Total number of polymer chains | 4 |
| Total formula weight | 50430.93 |
| Authors | Schubert, H.L.,Zhai, Q.,Hill, C.P. (deposition date: 2010-07-09, release date: 2010-07-21, Last modification date: 2024-11-27) |
| Primary citation | Schubert, H.L.,Zhai, Q.,Sandrin, V.,Eckert, D.M.,Garcia-Maya, M.,Saul, L.,Sundquist, W.I.,Steiner, R.A.,Hill, C.P. Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations. Proc.Natl.Acad.Sci.USA, 107:17951-17956, 2010 Cited by PubMed Abstract: HIV-1 and other enveloped viruses can be restricted by a host cellular protein called BST2/tetherin that prevents release of budded viruses from the cell surface. Mature BST2 contains a small cytosolic region, a predicted transmembrane helix, and an extracellular domain with a C-terminal GPI anchor. To advance understanding of BST2 function, we have determined a 2.6 Å crystal structure of the extracellular domain of the bacterially expressed recombinant human protein, residues 47-152, under reducing conditions. The structure forms a single long helix that associates as a parallel dimeric coiled coil over its C-terminal two-thirds, while the N-terminal third forms an antiparallel four-helix bundle with another dimer, creating a global tetramer. We also report the 3.45 Å resolution structure of BST2(51-151) prepared by expression as a secreted protein in HEK293T cells. This oxidized construct forms a dimer in the crystal that is superimposable with the reduced protein over the C-terminal two-thirds of the molecule, and its N terminus suggests pronounced flexibility. Hydrodynamic data demonstrated that BST2 formed a stable tetramer under reducing conditions and a dimer when oxidized to form disulfide bonds. A mutation that selectively disrupted the tetramer (L70D) increased protein expression modestly but only reduced antiviral activity by approximately threefold. Our data raise the possibility that BST2 may function as a tetramer at some stage, such as during trafficking, and strongly support a model in which the primary functional state of BST2 is a parallel disulfide-bound coiled coil that displays flexibility toward its N terminus. PubMed: 20880831DOI: 10.1073/pnas.1008206107 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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