Structural determinants for activity and specificity of the bacterial toxin LlpA.

TitleStructural determinants for activity and specificity of the bacterial toxin LlpA.
Publication TypeJournal Article
Year of Publication2013
AuthorsGhequire, M. G. K., A. Garcia-Pino, E. K. M. Lebbe, S. Spaepen, R. Loris, and R. De Mot
JournalPLoS Pathog
Date Published2013 Feb
KeywordsAnti-Bacterial Agents, Bacterial Toxins, Bacteriocins, Circular Dichroism, Crystallization, DNA Mutational Analysis, DNA, Bacterial, DNA, Recombinant, Microbial Sensitivity Tests, Protein Binding, Protein Structure, Tertiary, Pseudomonas putida, Structure-Activity Relationship, Substrate Specificity

Lectin-like bacteriotoxic proteins, identified in several plant-associated bacteria, are able to selectively kill closely related species, including several phytopathogens, such as Pseudomonas syringae and Xanthomonas species, but so far their mode of action remains unrevealed. The crystal structure of LlpABW, the prototype lectin-like bacteriocin from Pseudomonas putida, reveals an architecture of two monocot mannose-binding lectin (MMBL) domains and a C-terminal β-hairpin extension. The C-terminal MMBL domain (C-domain) adopts a fold very similar to MMBL domains from plant lectins and contains a binding site for mannose and oligomannosides. Mutational analysis indicates that an intact sugar-binding pocket in this domain is crucial for bactericidal activity. The N-terminal MMBL domain (N-domain) adopts the same fold but is structurally more divergent and lacks a functional mannose-binding site. Differential activity of engineered N/C-domain chimers derived from two LlpA homologues with different killing spectra, disclosed that the N-domain determines target specificity. Apparently this bacteriocin is assembled from two structurally similar domains that evolved separately towards dedicated functions in target recognition and bacteriotoxicity.

Alternate JournalPLoS Pathog.
PubMed ID23468636
PubMed Central IDPMC3585409