6BED
Crystal structure of VACV D13 in complex with Rifampicin
Summary for 6BED
| Entry DOI | 10.2210/pdb6bed/pdb |
| Related | 3SAM 3SAQ 6BEB 6BEC 6BEE 6BEF 6BEG 6BEH 6BEI |
| Descriptor | Scaffold protein D13, FORMIC ACID, 1,2-ETHANEDIOL, ... (5 entities in total) |
| Functional Keywords | viral protein, poxvirus, assembly, scaffolding protein, rifampicin resistance, immature virion |
| Biological source | Vaccinia virus WR (VACV) |
| Total number of polymer chains | 3 |
| Total formula weight | 188363.96 |
| Authors | Garriga, D.,Accurso, C.,Coulibaly, F. (deposition date: 2017-10-25, release date: 2018-07-18, Last modification date: 2023-10-04) |
| Primary citation | Garriga, D.,Headey, S.,Accurso, C.,Gunzburg, M.,Scanlon, M.,Coulibaly, F. Structural basis for the inhibition of poxvirus assembly by the antibiotic rifampicin. Proc. Natl. Acad. Sci. U.S.A., 115:8424-8429, 2018 Cited by PubMed Abstract: Poxviruses are large DNA viruses that cause disease in animals and humans. They differ from classical enveloped viruses, because their membrane is acquired from cytoplasmic membrane precursors assembled onto a viral protein scaffold formed by the D13 protein rather than budding through cellular compartments. It was found three decades ago that the antibiotic rifampicin blocks this process and prevents scaffold formation. To elucidate the mechanism of action of rifampicin, we have determined the crystal structures of six D13-rifamycin complexes. These structures reveal that rifamycin compounds bind to a phenylalanine-rich region, or F-ring, at the membrane-proximal opening of the central channel of the D13 trimer. We show by NMR, surface plasmon resonance (SPR), and site-directed mutagenesis that A17, a membrane-associated viral protein, mediates the recruitment of the D13 scaffold by also binding to the F-ring. This interaction is the target of rifampicin, which prevents A17 binding, explaining the inhibition of viral morphogenesis. The F-ring of D13 is both conserved in sequence in mammalian poxviruses and essential for interaction with A17, defining a target for the development of assembly inhibitors. The model of the A17-D13 interaction describes a two-component system for remodeling nascent membranes that may be conserved in other large and giant DNA viruses. PubMed: 30068608DOI: 10.1073/pnas.1810398115 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.75 Å) |
Structure validation
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