STRUCTURE OF THE FIRST C-2 DOMAIN OF SYNAPTOTAGMIN .1. A NOVEL CA2+/PHOSPHOLIPID-BINDING FOLD

C-2 domains are regulatory sequence motifs that occur widely in nature. Synaptotagmin I, a synaptic vesicle protein involved in the Ca2+ regulation of exocytosis, contains two C-2 domains, the first of which acts as a Ca2+ sensor. We now describe the three-dimensional structure of this C-2 domain at 1.9 Angstrom resolution in both the Ca2+-bound and Ca2+-free forms. The C-2 polypeptide forms an eight-stranded beta sandwich constructed around a conserved four-stranded motif designated as a C-2 key. Ca2+ binds in a cup-shaped depression between two polypeptide loops located at the N- and C-termini of the C-2-key motif.