Theoretical estimation of the calcium-binding constants for proteins from the troponin C superfamily based on a...

Proteins belonging to the TNC superfamily are known to be built of two, three, four, or six domains of closely similar amino acid sequences. Each domain binds no more than one calcium ion and shows a characteristic helix-loop-helix structure when in the calcium-bound state. Conformational properties of all the domains known so far have been analysed by us using a secondary structure prediction method (Garnier, J., Osguthorpe, D.J. & Robson, B. (1978). J. molec. Biol. 120, 97). Significant differences in distribution of residues predicted as being in the helical, beta-turn, and coil conformations have been found between the strongly, weakly, and non-binding domains. We could determine the ideal prediction pattern characteristic for the domains with the highest affinity for calcium. On the basis of our analysis and observations made by other authors we worked out a few simple rules which made it possible to compare conformational properties of a given domain with the ideal reference pattern and estimate, in this way, the Ca2+-binding constant of the domain. In native proteins the domains are known to be organized in pairs. The Ca2+-binding constant for a two-domain region could be evaluated from the sum of the estimation points attributed to each of its components. Using our method it is possible to predict the binding constants of typical domains and two-domain regins with a precision of one order of magnitude. Data on amino acid sequences and calcium-binding constants of all known proteins, believed to be the members of the TNC superfamily, have been reviewed. References to virtually all papers published on this subject before the end of 1987 are given.