Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

We report the crystal structure of the Escherichia coli TolB-Pal complex, a protein-protein complex involved in maintaining the integrity of the outer membrane (OM) in all Gram-negative bacteria that is parasitized by colicins (protein antibiotics) to expedite their entry into cells. Nuclease colicins competitively recruit TolB using their natively disordered regions (NDRs) to disrupt its complex with Pal, which is thought to trigger translocation of the toxin across a locally destabilized OM. The structure shows induced-fit binding of peptidoglycan-associated lipoprotein (Pal) to the beta-propeller domain of TolB causing the N-terminus of one of its alpha-helices to unwind and several residues to undergo substantial changes in conformation. The resulting interactions with TolB are known to be essential for the stability of the complex and the bacterial OM. Structural comparisons with a TolB-colicin NDR complex reveal that colicins bind at the Pal site, mimicking rearranged Pal residues while simultaneously appearing to block induced-fit changes in TolB. The study therefore explains how colicins recruit TolB in the bacterial periplasm and highlights a novel binding mechanism for a natively disordered protein.

Original publication




Journal article


J Am Chem Soc

Publication Date





4800 - 4807


Amino Acids, Bacterial Outer Membrane Proteins, Crystallography, X-Ray, Escherichia coli Proteins, Hydrogen Bonding, Lipoproteins, Models, Molecular, Molecular Mimicry, Peptidoglycan, Periplasmic Proteins, Protein Binding, Protein Denaturation, Protein Structure, Quaternary, Protein Transport, Thermodynamics