Chemistry and biology of the S-100 protein.

The S-100 protein is specific for the nervous system and, being present in all vertebrates, shows a high degree of stability of structure during evolution. In adult animals it is primarily localized to glial elements, although there is some evidence that a small proportion may be present in neuronal nuclei or their plasma membranes. During development it is synthesized rapidly at a relatively late period of differentiation of the nervous system. In glioma cell cultures there is a control mechanism that seems to involve some kind of signal at the external surface of the plasma membrane, possibly specific cell-cell contact, to stimulate S-100 synthesis. All of these biological properties of S-100 suggest that it is connected with some specific essential function that is common to the nervous system of all vertebrates. Several chemical properties of S-100 provide clues to this function. It is an unusually acidic and soluble protein and, in the absence of Ca2+, has no detectable hydrophobic regions accessible to solvent. It is capable of specifically binding Ca2+, a process that causes S-100 to undergo a conformational change that exposes a hydrophobic region to the solvent and stimulates binding of S-100 to membranes. The conformational change and the membrane-binding properties are reversible when Ca2+ is removed and are antagonized by monovalent cations such as K+ and Na+. These chemical properties suggest that S-100 may, as part of its function in the nervous system, be bound to some hydrophobic site, possibly a membrane, and that the extent of this binding is regulated by concentrations of Ca2+, K+ and Na+. If this is true, then it is important, as the next step in working out its function, to discover the exact site where S-100 binds in the nervous system.