Tardigrades are microscopic aquatic animals that exhibit remarkable resistance to environmental stress, including radiation, cryogenic temperatures and desiccation. Although the origins of this extremotolerance are poorly understood, intrinsically disordered proteins are known to play a crucial role, allowing tardigrades to survive in a dormant state for long periods of time (years), and to function normally upon return to ambient conditions. Researchers from the Protein Dynamics and Flexibility by NMR Group (IBS/FDP) previously demonstrated that one such protein undergoes a reversible conformational transition in response to environmental change, self-assembling to form a fibrous hydrogel a transition thought to be integral to tardigrade stress resistance.
Thanks to collaboration between the FDP and MEM groups of the IBS and ESRF (Max Nanao), researchers used an integrated approach, combining X-ray crystallography with NMR, atomic force and electron microscopy, as well as disorder modelling, to determine the atomic structure of the fibrils. Individual fibrils are formed from a single extended helix that dimerises via two distinct interfaces situated on alternate faces of the helix. These two interfaces mediate a unique mode of assembly of the continuous fibril. Fibrils interact in a pairwise manner, apparently via their disordered domains, to form straight fibres.
This study will inform further investigation of the molecular basis of stress resistance in tardigrades, while providing new avenues for peptide pharmaceuticals, drug delivery, preservation of biomass or design of stress-tolerant proteins.
Fibril Structure of Desiccation-Protective Tardigrade Protein CAHS-8. Malki A, Teulon JM, Mikkola EA, Maurin D, Pellequer JL, Nanao MH, Blackledge M. Angewandte Chemie International Edition 2025 ; e19912.
Contact : Martin Blackledge (IBS/Protein Dynamics and Flexibility by NMR Group)