A change-in-hand mechanism for S100 signalling

S100 proteins are a group of small dimeric calcium-binding proteins making up a large subclass of the EF-hand family of calcium-binding proteins. Memb ers of this family of proteins have been proposed to act as intracellular c alcium modulatory proteins in a fashion analogous to that of the EF-hand se nsor proteins troponin-C and calmodulin. Recently, NMR spectroscopy has pro vided the three-dimensional structures of the S100 family members S100A6 an d S100B in both the apo- and calcium-bound forms. These structures have all owed for the identification of a novel calcium-induced conformational chang e termed the change-in-hand mechanism. Helix III of the C-terminal calcium- binding loop changes its helix-helix interactions (or handness) with the re mainder of the molecule primarily owing to the reorientation of the backbon e in an effort to coordinate the calcium ion. This reorientation of helix I II exposes several residues in the C-terminus and linker regions of S100B r esulting in the formation of a hydrophobic patch surrounded be a number of acidic residues. This site is the proposed region for protein-protein recog nition.