Solution structures of chicken parvalbumin 3 in the Ca2+-free and Ca2+-bound states.

Birds express two β-parvalbumin isoforms, parvalbumin 3 and avian thymic hormone (ATH). Parvalbumin 3 from chicken (CPV3) is identical to rat β-parvalbumin (β-PV) at 75 of 108 residues. CPV3 displays intermediate Ca2+ affinity—higher than that of rat β-parvalbumin, but lower than that of ATH. As in rat β-PV, the attenuation of affinity is associated primarily with the CD site (residues 41–70), rather than the EF site (residues 80–108). Structural data for rat - and β-parvalbumins suggest that divalent ion affinity is correlated with the similarity of the unliganded and Ca2+-bound conformations. We herein present a comparison of the solution structures of Ca2+-free and Ca2+-bound CPV3. Although the structures are generally similar, the conformations of residues 47 to 50 differ markedly in the two protein forms. These residues are located in the C helix, proximal to the CD binding loop. In response to Ca2+ removal, F47 experiences much greater solvent accessibility. The side-chain of R48 assumes a position between the C and D helices, adjacent to R69. Significantly, I49 adopts an interior position in the unliganded protein that allows association with the side-chain of L50. Concomitantly, the realignment of F66 and F70 facilitates their interaction with I49 and reduces their contact with residues in the N-terminal AB domain. This reorganization of the hydrophobic core, although less profound, is nevertheless reminiscent of that observed in rat β-PV. The results lend further support to the idea that Ca2+ affinity correlates with the structural similarity of the apo- and bound parvalbumin conformations. Proteins 2011. © 2010 Wiley-Liss, Inc.