| Summary: | The experimental availability of a variety of strains of Euplotes nobilii and E. raikovi, which are species phylogenetically closely related yet ecologically separated (the former inhabiting Antarctic and Arctic waters, and the latter inhabiting temperate waters), permitted us to carry out a comparative study of the NMR solution structures that distinguish the psychrophilic (cold-loving) and the mesophilic pheromone families of these two species. The molecular structures of all the members of the two families show in common a tight conservation of a three-helix bundle core, which ensures long-lasting structural integrity and biological activity to these water-borne signal proteins in their natural marine environment. To this conserved scaffold, each pheromone shows to have added a set of individual structural traits primarily committed to confer specificity on its autocrine (mitogenic) and paracrine (sexual) signaling activities. These traits mainly involve variations in the length and regularity of the three helices, as well as in the shape and orientation of the carboxy-terminal segment. At inter-species level, the E. nobilii pheromone family is clearly distinguished by a complex of structural modifications that appear to have been evolved in functional correlation with cold-adaptation. Most relevant are the extension of polypeptide segments devoid of regular secondary structures, a unique distribution of polar and hydrophobic amino acids, the presence of solvent-exposed clusters of negatively charged amino acid side chains, and a primary role of aromatic residues in anchoring regions of the molecular architecture. Overall these cold-adaptive modifications make the psychrophilic pheromone family of E. nobilii an elegant example of how signal molecules combine a high global stability of their three-dimensional structures with sufficient levels of local structural plasticity for an efficient functioning at physiologically low temperatures
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