Comparison of S100b protein with calmodulin: interactions with melittin and microtubule-associated .tau. proteins and inhibition of phosphorylation of .tau. proteins by protein kinase C

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Abstract
To gauge similarities between S100b protein and calmodulin, interactions were observed between S100b and melittin and between S100b and .tau., the microtubule-associated proteins. The interaction of melittin with S100b protein in the presence and absence of calcium was studied by fluorescence polarization, UV differences spectroscopy, and sulfhydryl derivatization. Whether calcium was present or not in the solution, melittin and S100b form a complex of molar ratios up 2:1. Further binding of melittin occurred, but it resulted in precipitation of S100b, as is true of the corresponding case of melittin binding to calmodulin. In the absence of calcium, the interaction of melittin and S100b shielded the tryptophan (Trp) of the former protein and exposed cysteine-84.beta. (Cys-84.beta.) of the latter protein, leaving the tyrosine-16.beta. (Tyr-16.beta.) of S100b unaffected. Calcium addition to the complex partially restored the exposure of Trp of melittin and caused changes in the environment of Tyr-16.beta. (unlike the environmental changes induced for Tyr-16.beta. by calcium in the absence of melittin). The conformational changes induced in S100b by interaction with melittin increased its affinity for calcium and offset the inhibition of calcium binding otherwise observed in the presence of potassium ions. This corroborated the previous finding that S100b affinity for calcium greatly depends on the protein conformation. The phenomena described above are similar to the interactions of melittin with calmodulin and thus suggest that S100b and calmodulin have a common structural domain not only that binds melittin but also that may interact with common target proteins. In support of this suggestion is our observation that S100b, as previously reported for calmodulin, binds to the microtubule-associated protein .tau. in the presence of calcium, a fact that could explain their common calcium-dependent effects on microtubule assembly. Complex formation of .tau. with S100b or calmodulin was confirmed when we discovered that both S100b and calmodulin inhibit the calcium/phospholipid-dependent phosphorylation of .tau. proteins by protein kinase C by interacting with the substrate rather than with the kinase itself.

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