SummaryA complete molecular model of blood coagulation factor Va (FVa) bound to anticoagulant activated protein C (APC) and to a phospholipid membrane was constructed. The three homologous A domains and the two homologous C domains of FVA were modeled based on the X-ray crystallographic structures of ceruloplasmin and C2 domain of factor V, respectively. The final arrangement of the five domains in the complete FVa model bound to a membrane incorporated extensive published experimental data. FVa binds the phospholipid membrane through its C2 domain while the A-domain trimer is located from 40 through 100 Å above the membrane plane. From our model we infer a probable role for metal ions at the interface between FVa light and heavy chains, provide an explanation for the slower APC cleavage at Arg306 relative to Arg506, and predict specific interactions between positively and negatively charged exosites in APC and FVa, respectively.

Tardigrades are remarkable for their ability to survive harsh stress conditions as diverse as extreme temperature and desiccation. The molecular mechanisms that confer this unusual resistance to physical stress remain unknown. Recently, tardigrade‐unique intrinsically disordered proteins have been shown to play an essential role in tardigrade anhydrobiosis. Here, we characterize the conformational and physical behaviour of CAHS‐8 from Hypsibius exemplaris. NMR spectroscopy reveals that the protein comprises an extended central helical domain flanked by disordered termini. Upon concentration, the protein is shown to successively form oligomers, long fibres, and finally gels constituted of fibres in a strongly temperature‐dependent manner. The helical domain forms the core of the fibrillar structure, with the disordered termini remaining highly dynamic within the gel. Soluble proteins can be encapsulated within cavities in the gel, maintaining their functional form. The ability to reversibly form fibrous gels may be associated with the enhanced protective properties of these proteins.

Tardigrades are remarkable for their ability to survive harsh stress conditions as diverse as extreme temperature and desiccation. The molecular mechanisms that confer this unusual resistance to physical stress remain unknown. Recently, tardigrade‐unique intrinsically disordered proteins have been shown to play an essential role in tardigrade anhydrobiosis. Here, we characterize the conformational and physical behaviour of CAHS‐8 from Hypsibius exemplaris. NMR spectroscopy reveals that the protein comprises an extended central helical domain flanked by disordered termini. Upon concentration, the protein is shown to successively form oligomers, long fibres, and finally gels constituted of fibres in a strongly temperature‐dependent manner. The helical domain forms the core of the fibrillar structure, with the disordered termini remaining highly dynamic within the gel. Soluble proteins can be encapsulated within cavities in the gel, maintaining their functional form. The ability to reversibly form fibrous gels may be associated with the enhanced protective properties of these proteins.