Rearrangements under confinement lead to increased binding energy of Synaptotagmin-1 with anionic membranes in Mg and Ca.

Synaptotagmin-1 (Syt1) is the primary calcium sensor (Ca ) that mediates neurotransmitter release at the synapse. The tandem C2 domains (C2A and C2B) of Syt1 exhibit functionally critical, Ca -dependent interactions with the plasma membrane. With the surface forces apparatus, we directly measure the binding energy of membrane-anchored Syt1 to an anionic membrane and find that Syt1 binds with ~6 k T in EGTA, ~10 k T in Mg and ~18 k T in Ca . Molecular rearrangements measured during confinement are more prevalent in Ca and Mg and suggest that Syt1 initially binds through C2B, then reorients the C2 domains into the preferred binding configuration. These results provide energetic and mechanistic details of the Syt1 Ca -activation process in synaptic transmission.

© 2018 Federation of European Biochemical Societies.