Secondary-structure predictions of calcium-binding proteins.

The known tertiary structure of carp muscle parvalbumin is consistent with an "EF-hand" architecture (helix-loop-helix) for each calcium-ion binding site. Primary-sequence alignments have indicated four EF hands in rabbit skeletal muscle troponin C and in rabbit myosin alkali light chains. Five secondary-structure prediction methods, based on amino acid sequence only, have been fully computerized and used to calculate joint prediction histograms for several calcium-binding proteins. The joint histogram can suggest directly the extent and sequence of the helical- and loop-structural elements, as well as any secondary structural distortions or evolutionary developments. Since the histogram predicted well the length and sequence of secondary structural elements in carp muscle parvalbumin, it seemed reasonable to calculate the joint distribution for other proteins that might bind calcium through the EF-hand configuration. The histograms indicated the four EF-hand regions speculated fro rabbit skeletal muscle troponin C but suggested only three such hands in bovine cardiac muscle troponin C and with a distorted fourth hand. Considerable secondary structural distortion is postulated for the alkali light chains. Possible EF configurations consistent with the histogram results are speculated for Escherichia coli acyl-carrier protein and bovine prothrombin fragment 1, which have been shown to bind calcium. The secondary-structure-prediction algorithms appear to be a useful adjunct to sequence-alignment techniques, especially in cases where the primary sequence homology is weak or the evolutionary distance is large.