Fibril Structure of Desiccation‐Protective Tardigrade Protein CAHS‐8

Abstract

Abstract Cytosolic Abundant Heat‐Soluble (CAHS) proteins are thought to be responsible for protection of tardigrades against conditions of extreme environmental stress, in particular desiccation. Hypsibius exemplaris CAHS‐8 is intrinsically disordered in solution, undergoing conformational transformation as a function of stress, assembling into fibres that form a hydrogel. Here we present the crystal structure of the fibrils of CAHS‐8, comprising a single 101 residue‐long helix, forming an atypical 90 amino‐acid coiled‐coil dimer exhibiting non‐canonical periodicities and assembling into fibrils via a second coiled coil interface associating adjacent dimers via the opposing face of the helix. Combination with electron microscopy, atomic force microscopy and disorder modelling provides structural insight into the details of this assembly that is essential for cell survival. Individual fibrils appear to interact in a pairwise manner, possibly via their intrinsically disordered tails, forming straight fibres.