5I97
Structural analysis and inhibition of TraE from the pKM101 type IV secretion system
Summary for 5I97
| Entry DOI | 10.2210/pdb5i97/pdb |
| Descriptor | Conjugal transfer protein (2 entities in total) |
| Functional Keywords | bacterial secretion, type iv secretion, virb, protein transport |
| Biological source | Escherichia coli |
| Total number of polymer chains | 4 |
| Total formula weight | 75272.42 |
| Authors | Casu, B.,Sygusch, J.,Baron, C. (deposition date: 2016-02-19, release date: 2016-09-28, Last modification date: 2023-09-27) |
| Primary citation | Casu, B.,Smart, J.,Hancock, M.A.,Smith, M.,Sygusch, J.,Baron, C. Structural Analysis and Inhibition of TraE from the pKM101 Type IV Secretion System. J.Biol.Chem., 291:23817-23829, 2016 Cited by PubMed Abstract: Gram-negative bacteria use type IV secretion systems (T4SSs) for a variety of macromolecular transport processes that include the exchange of genetic material. The pKM101 plasmid encodes a T4SS similar to the well-studied model systems from Agrobacterium tumefaciens and Brucella suis Here, we studied the structure and function of TraE, a homolog of VirB8 that is an essential component of all T4SSs. Analysis by X-ray crystallography revealed a structure that is similar to other VirB8 homologs but displayed an altered dimerization interface. The dimerization interface observed in the X-ray structure was corroborated using the bacterial two-hybrid assay, biochemical characterization of the purified protein, and in vivo complementation, demonstrating that there are different modes of dimerization among VirB8 homologs. Analysis of interactions using the bacterial two-hybrid and cross-linking assays showed that TraE and its homologs from Agrobacterium, Brucella, and Helicobacter pylori form heterodimers. They also interact with heterologous VirB10 proteins, indicating a significant degree of plasticity in the protein-protein interactions of VirB8-like proteins. To further assess common features of VirB8-like proteins, we tested a series of small molecules derived from inhibitors of Brucella VirB8 dimerization. These molecules bound to TraE in vitro, docking predicted that they bind to a structurally conserved surface groove of the protein, and some of them inhibited pKM101 plasmid transfer. VirB8-like proteins thus share functionally important sites, and these can be exploited for the design of specific inhibitors of T4SS function. PubMed: 27634044DOI: 10.1074/jbc.M116.753327 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.441 Å) |
Structure validation
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