Human S100A14 is a member of the EF-hand calcium-binding protein family that has
only recently been described in terms of its functional and pathological
properties. The protein is overexpressed in a variety of tumor cells and it has
been shown to trigger receptor for advanced glycation end products
(RAGE)-dependent signaling in cell cultures. The solution structure of
homodimeric S100A14 in the apo state has been solved at physiological
temperature. It is shown that the protein does not bind calcium(II) ions and
exhibits a "semi-open" conformation that thus represents the
physiological structure of the S100A14. The lack of two ligands in the canonical
EF-hand calcium(II)-binding site explains the negligible affinity for
calcium(II) in solution, and the exposed cysteines and histidine account for the
observed precipitation in the presence of zinc(II) or copper(II) ions.
