S100 Proteins: From Purification to Functions

Abstract

The first description of S100 proteins was made by B. W. Moore who initially characterized a group of abundant low-molecular-weight (10-12) acidic (pH 4.0-5.0) proteins that were enriched in the nervous system (1). Their name derives from their unusual solubility in 100% ammonium sulfate at nearly neutral pH (7.0-7.5). The S100 fraction, isolated from brain, was subjected to intensive investigation, and it was then demonstrated that there were, in fact, multiple protein species. Two distinct S100 proteins were first characterized, the S100A1 (S100αα) and S100B (S100ββ) by Isobe and co-workers (2). Over the past few years, this S100 protein family has expanded with the description of at least 17 other S100 proteins (3). All the characterized members of the S100 protein family have significant physicochemical properties in common. They show different degrees of homology, ranging from 25-65% identity at the amino acid level. In solution, S100 proteins associate as homodimers, but they are also prone to form heterodimers by combination with other S100 species (4). The S100 proteins contain two EF-hand calcium-binding sites. When these sites are filled with Ca2+, a number of physicochemical and structural properties of the proteins are altered. Calcium binding induces conformational changes that result in the exposure of hydrophobic patches to solvent, allowing hydrophobic interactions with target proteins, hydrophobic dyes, and hydrophobic matrix (5).