A BROAD range of organisms and tissues contain 14-3-3 proteins, which have been associated with many diverse functions including critical roles in signal transduction pathways, exocytosis and cell cycle regulation(1). We report here the crystal structure of the human T-cell 14-3-3 isoform (tau) dimer at 2.6 Angstrom resolution. Each monomer (M(r) 28K) is composed of an unusual arrangement of nine antiparallel alpha-helices organized as two structural domains. The dimer creates a large, negatively charged channel approximately 35 Angstrom broad, 35 Angstrom wide and 20 Angstrom deep. Overall, invariant residues line the interior of this channel whereas the more variable residues are distributed on the outer surface. At the base of this channel is a 16-residue segment of 14-3-3 which has been implicated in the binding of 14-3-3 to protein kinase C.