The Zn2+ and Ca2+‐binding S100B and S100A1 proteins: beyond the myths

The S100 genes encode a conserved group of 21 vertebrate‐specific EF‐hand calcium‐binding proteins. Since their discovery in 1965, S100 proteins have remained enigmatic in terms of their cellular functions. In this review, we summarize the calcium‐ and zinc‐binding properties of the dimeric S100B and S100A1 proteins and highlight data that shed new light on the extracellular and intracellular regulation and functions of S100B. We point out that S100B and S100A1 homodimers are not functionally interchangeable and that in a S100A1/S100B heterodimer, S100A1 acts as a negative regulator for the ability of S100B to bind Zn²⁺. The Ca²⁺ and Zn²⁺‐dependent interactions of S100B with a wide array of proteins form the basis of its activities and have led to the derivation of some initial rules for S100B recognition of protein targets. However, recent findings have strongly suggested that these rules need to be revisited. Here, we describe a new consensus S100B binding motif present in intracellular and extracellular vertebrate‐specific proteins and propose a new model for stable interactions of S100B dimers with full‐length target proteins. A chaperone‐associated function for intracellular S100B in adaptive cellular stress responses is also discussed. This review may help guide future studies on the functions of S100 proteins in general.     

The vacuolar Ca2+/H+ exchanger Vcx1p/Hum1p tightly controls cytosolic Ca2+ levels in S. cerevisiae.

It is well established that the vacuole plays an important role in the cellular adaptation to growth in the presence of elevated extracellular Ca2+ concentrations in Saccharomyces cerevisiae. The Ca2+ ATPase Pmc1p and the Ca2+/H+ exchanger Vcx1p/Hum1p have been shown to facilitate Ca2+ sequestration into the vacuole. However, the distinct physiological roles of these two vacuolar Ca2+ transporters remain uncertain. Here we show that Vcx1p can rapidly sequester a sudden pulse of cytosolic Ca2+ into the vacuole, while Pmc1p carries out this function much less efficiently. This finding is consistent with the postulated role of Vcx1p as a high capacity, low affinity Ca2+ transporter and suggests that Vcx1p may act to attenuate the propagation of Ca2+ signals in this organism.