K-081. Different Recruitment of the TolB Translocation Portal by the Natively Disordered Domain of Colicins

Y. Zhang, M. Vankemmelbeke, C. Li, M. Paoli, C. N. Penfold, R. James;
Univ. of Nottingham, Nottingham, UNITED KINGDOM.

Colicins are multidomain protein antibiotics that consist of three domains, an N-terminal translocation domain, a central receptor-binding domain and a C-terminal cytotoxic domain. Group A colicins, such as colicins E9 and A, use the tol-dependent translocation system that includes TolQ, TolR, TolA, TolB and Pal proteins. Binding of either colicin to TolB initiates translocation of the cytoxic domain across the outer membrane and into the cytoplasmic membrane, for colicin A, or further into the cytoplasm, as is the case for the DNase domain of colicin E9. The N-terminal translocation domain of colicins contain natively disordered regions (NDR) that are implicated in their interaction with Tol proteins. The differences between colicin A (pore-former) and colicin E9 (DNase) are intriguing and may give clues about the mechanism of translocation and/or the mechanism by which they reach their cellular target in the cytoplasmic membrane and in the cytoplasm respectively. We have used a variety of techniques to address the different recruitment of TolB by colicin A and colicin E9. Structure determination of the TolB box containing N-terminal 107 amino acids of colicinA bound to TolB highlights differences between the interactions of the NDR’s of colicin A and colicin E9 with TolB. Understanding the colicin translocation mechanism provides information about protein-protein interactions of NDRs and may be useful in developing new antibiotics.

172/K. Genetic & Biochemical Regulation of Metabolic Pathways

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