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+ reg ulation of exocytosis, contains two C-2 domains, the first of which ac ts as a Ca2+ sensor. We now describe the three-dimensional structure o f this C-2 domain at 1.9 Angstrom resolution in both the Ca2+-bound an d Ca2+-free forms. The C-2 polypeptide forms an eight-stranded beta sa ndwich constructed around a conserved four-stranded motif designated a s a C-2 key. Ca2+ binds in a cup-shaped depression between two polypep tide loops located at the N- and C-termini of the C-2-key motif.