Solution structure and dynamics of human S100A14
Ivano Bertini, Valentina Borsi, Linda Cerofolini, Soumyasri Das Gupta, Marco Fragai and Claudio Luchinat [1]
Molecular Tour
Human S100A14 is a member of the EF-hand calcium-binding protein family that has only recently been described in 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 protein has a high degree of sequence homology with S100A13 although it exhibits a negligible affinity for calcium(II) ions and undergoes aggregation and precipitation in the presence of zinc(II) or copper(II) ions. The lack of two ligands in the canonical EF-hand calcium(II)-binding site explains the negligible affinity for calcium(II) in solution, while the exposed cysteines and histidine account for the observed precipitation in the presence of zinc(II) or copper(II) ions. The solution structure of homodimeric S100A14 in the apo state at physiological temperature shows close structural similarities with the C-terminal domain of the myosin light chains and folds in a ‘semi-open’ conformation, with helices III and IV showing a X-shaped offset arrangement and helices II and III showing a high number of interactions creating a V-shaped arrangement.
The most remarkable feature of this structural conformation involves the packing of the helices that is reduced with respect to the ‘closed’ structures of the S100 proteins but is still sizably larger than the corresponding ‘open’ structures. At the same time, the analysis of the electrostatic potential surface suggests that the protein is permanently activated and it is not calcium(II) regulated.
