5i97
From Proteopedia
Structural analysis and inhibition of TraE from the pKM101 type IV secretion system
Structural highlights
FunctionPublication Abstract from PubMedGram-negative bacteria use type IV secretion systems for a variety of macromolecular transport processes that include the exchange of genetic material. The pKM101 plasmid encodes a type IV secretion system 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 T4SS. 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 crosslinking 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 type IV secretion system function. Structural analysis and inhibition of TraE from the pKM101 type IV secretion system.,Casu B, Smart J, Hancock MA, Smith M, Sygusch J, Baron C J Biol Chem. 2016 Sep 15. pii: jbc.M116.753327. PMID:27634044[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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