Crystal Structure of the Escherichia coli Fic Toxin-Like Protein in Complex with Its Cognate Antitoxin.

摘要: FIC domain proteins mediate post-translational modifications of target proteins, which typically results in their inactivation. Depending on the conservation crucial active site residues, fold serves as structural scaffold for various enzymatic activities, mostly adenylylation. The founding member vast Fic protein family, EcFicT, was identified Escherichia coli some time ago. G55R point mutant EcFicT displays "filamentation induced by cAMP" (Fic) phenotype at high 3',5'-cyclic adenosine monophosphate (cAMP) concentrations and elevated temperature, but underlying molecular mechanism any putative biochemical activity have remained unknown. belongs to class I toxin that are encoded together with a small inhibitory (antitoxin), named EcFicA E. coli. Here, we report crystal structures two EcFicT/EcFicA complexes (EcFicTG55RA EcFicTAE28G) both showing close resemblance structure AMP-transferase VbhT from Bartonella schoenbuchensis complex its cognate antitoxin VbhA. However, differences compared other AMP-transferases rationalize lack evidence adenylylation activity. Comprehensive bioinformatic analysis suggests has evolved canonical acquired conserved binding yet be discovered novel substrate. mutation no effect or thermal stability such basis associated remains elusive. We anticipate this will inspire further experimental analyses order characterize help revealing physiological role.