EF-HANDS AT ATOMIC-RESOLUTION - THE STRUCTURE OF HUMAN PSORIASIN (S100A7) SOLVED BY MAD PHASING

Background: The S100 family consists of small acidic proteins, belongi ng to the EF-hand class of calcium-binding proteins, They are primaril y regulatory proteins, involved in cell growth, cell structure regulat ion and signal transduction. Psoriasin (S100A7) is an 11.7 kDa protein that is highly upregulated in the epidermis of patients suffering fro m the chronic skin disease psoriasis. Although its exact function is n ot known, psoriasin is believed to participate in the biochemical resp onse which follows transient changes in the cellular Ca2+ concentratio n. Results: The three-dimensional structure of holmium-substituted pso riasin has been determined by multiple anomalous wavelength dispersion (MAD) phasing and refined to atomic resolution (1.05 Angstrom), The s tructure represents the most accurately determined structure of a calc ium-binding protein. Although the overall structure of psoriasin is si milar to those of other S100 proteins, several important differences e xist, mainly in the N-terminal EF-hand motif that contains a distorted loop and lacks a crucial calcium-binding residue. it is these minor d ifferences that may account for the different specificities among memb ers of this family. Conclusions: The structure of human psoriasin reve als that this protein, in contrast to other S100 proteins with known s tructure, is not likely to strongly bind more than one calcium ion per monomer. The present study contradicts the idea that calcium binding induces large changes in conformation, as suggested by previously dete rmined structures of apo forms of S100 proteins. The substitution of C a2+ ions in EF-hands by lanthanide ions may provide a general vehicle for structure determination of S100 proteins by means of MAD phasing.