CRYSTAL-STRUCTURE OF THE C-TERMINAL TETRAD REPEAT FROM SYNEXIN (ANNEXIN-VII) OF DICTYOSTELIUM-DISCOIDEUM

Synexin (annexin VII) is a cytosolic Ca2+-binding protein that promote s membrane fusion and forms voltage-regulated ion channels in artifici al and natural membranes. The crystal structure of the C-terminal tetr ad repeat from recombinant synexin (annexin VII) of Dictyostelium disc oideum was solved to 2.45 Angstrom resolution. The protein crystallize d in a dimeric form with two molecules joined face-to-face by their co nvex sides. Mainly hydrogen bonds and van der Waals contacts are invol ved in dimer formation, while not Ca2+ is bound to the conserved Ca2+- binding sites. The truncated N terminus is folded into a short antipar allel P-sheet, from which the side-chain of Tyr111 penetrates sideways into the central, hydrophilic pore and may directly affect the ion ch annel activity. Ln order to investigate the structure of the missing N -terminal domain, we synthesized a 37-membered peptide of the N-termin al tail, (GYPPQQ)(6)G. CD and NMR studies showed a random coil conform ation of the peptide in solution, suggesting for the synexin N terminu s the lack of a well-ordered, three-dimensional fold. (C) 1997 Academi c Press Limited.