A dramatic protein fold switch powers a bactericidal nanomachine
Year: 2026
Type: preprint
Abstract: Fold switching, where a protein region interconverts between entirely distinct three-dimensional structures, is emerging as vital for certain protein functions. Here, we report a remarkable example in the F7 pyocin, a phage tail-like bactericidal nanomachine. Cryogenic electron microscopy and tomography reveal that a 163-residue segment of the central tail fiber undergoes a dramatic transition-from a trimeric α-helical coiled-coil to a triangular β-prism-upon binding to the bacterial cell surface. This massive fold switch remodels the tail tip, ejects the internal tape measure protein, and drives membrane puncture. Site-directed mutations that selectively destabilize the β-prism conformation completely abolish bactericidal activity without impairing particle assembly, implying that the energy released during this transition powers penetration. AlphaFold-based analyses further predict similar large-scale coiled-coil to β-prism switches in diverse non-contractile phage tails. This discovery reveals a sophisticated, ATP-independent strategy for microbial warfare and opens exciting possibilities for engineering next-generation bacteriocins to combat multidrug-resistant pathogens.
Language: English
Subfield: Ecology
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
Awards: In situ atomic structures of the Kaposi's sarcoma-associated herpesvirus portal-terminase complex and glycoproteins, Direct Detection Device for atomic resolution cryoEM of macromolecular complexes, Initiation of Phage Infection, High-throughput electron cryo-microscope, Structure-Function Relationships in the Spirochetal Flagellar Motor, High-Resolution CryoEM Reconstruction of Large Complexes
OpenAlex ID: W7126274654