{Reference Type}: Journal Article
{Title}: In search for globally disordered apo-parvalbumins: Case of parvalbumin β-1 from coho salmon.
{Author}: Vologzhannikova AA;Khorn PA;Kazakov AS;Ismailov RG;Sokolov AS;Uversky VN;Permyakov EA;Permyakov SE;
{Journal}: Cell Calcium
{Volume}: 67
{Issue}: 0
{Year}: 11 2017
{Factor}: 4.69
{DOI}: 10.1016/j.ceca.2017.08.011
{Abstract}: Parvalbumin (PA) is a classical EF-hand calcium-binding protein of muscle, neuronal, and other tissues, and a major fish allergen. Although certain apo-PAs lack tertiary structure, functional implications of that feature and its structural prerequisites remain unclear. In a search for unstable PAs, we probed conformational stability of parvalbumin β-1 from coho salmon (csPA), a cold water fish species, using circular dichroism, scanning calorimetry, hydrophobic probe fluorescence, limited proteolysis, chemical crosslinking and dynamic light scattering techniques. Apo-csPA is shown to be mainly monomeric protein with markedly disorganized secondary structure and lack of rigid tertiary structure. Examination of per-residue propensity for intrinsic disorder in the PA groups with either folded or unfolded apo-form using the average PONDR® VSL2P profiles revealed that the N-terminal region that includes α-helix A, AB-loop and N-terminal half of α-helix B is predicted to be less ordered in PAs with disordered apo-state. Application of the structural criteria developed for discrimination of disordered PAs indicate that the latter comprise about 16-19% of all PAs. We show that structural instability of apo-β-PA serves as a hallmark of elevated calcium affinity of the protein. Therefore, the successful predictions of unstable apo-PAs might facilitate search for PAs with maximal calcium affinity and possibly serving as calcium sensors.