Building coiled coils with polar cores

Abstract

Abstract Coiled coils are formed by α‐helices winding around each other into superhelical bundles. They are characterized by a specific geometry of interaction, called knobs‐into‐holes, in which residues in the core of the structure mesh regularly along a seam that runs the length of the helices. While these residues are predominantly hydrophobic, hydrophilic residues occur occasionally. In dimeric coiled coils, their sidechains are often sufficiently long to allow the head‐groups to extend out of the core and be solvated by water, but in trimeric and tetrameric coiled coils, they often cannot gain access to solvent and instead point inward, coordinating water molecules and ions along the central axis of the coiled coil. Building on this insight, we have used sequence motifs derived from trimeric autotransporter adhesins to design coiled‐coil sequences that lack hydrophobic sidechains for three or more consecutive heptads. Their crystal structures illustrate the strategies for accommodating extended stretches of hydrophilic residues within the coiled‐coil fold, which are confidently predicted as intrinsically disordered, raising questions about the actual structure of such proteins in their native environment.

The authors' abstract, as published at the source. Protein Science, 2026 · DOI ↗