Enzymatic E-colicins Bind to Their Target Receptor BtuB by Presentation of a Small Binding Epitope on a Coiled-coil Scaffold*

Toxins and viruses often initiate their attacks by bind-ing to specific proteins on the surfaces of target cells. Bacterial toxins (e.g. bacteriocins) and viruses (bacteri-ophages) targeting Gram-negative bacteria typically bind to outer membrane proteins. Bacterial E-colicins target Escherichia coli by binding to the outer mem-brane cobalamin transporter BtuB. Colicins are tripar-tite molecules possessing receptor-binding, transloca-tion, and toxin domains connected by long coiled-coil -helices. Surprisingly, the crystal structure of colicin E3 does not possess a recognizable globular fold in its receptor-binding domain. We hypothesized that the binding epitope of enzymatic E-colicins is a short loop connecting the two -helices that comprise the coiled-coil region and that this flanking coiled-coil regio