(A) X-ray structure of Syt1C2AB fitted into the EM density map of the Syt1C2AB coated monolayer tubes [Adapted from (Wang et al., 2014)] shows that C2B domain (gray) mediates both the membrane (yellow) association and the ring assembly and C2A domain (cyan) projects away from the ring. Surface representation of the tube is sectioned to the thickness of a single strand of the 4-start helix to reveal the shape of individual asymmetric unit. (B) Organization of the C2B domain in the Syt1 ring oligomer shows that the PIP2 binding polylysine motif (K326, K327, blue) are packed against the membrane surface, which holds back the Ca2+ binding site/loop (red) of C2B from the membrane and it localizes to the protein-protein interface involved in ring formation. This arrangement explains the Ca2+-sensitivity of the Syt1 rings as Ca2+ binding would include reorientation of the C2B domain from the ring geometry. Further, in this model, the recently identified (Zhou et al., 2015) primary SNARE binding interface on the C2B (R281, E295, Y338, R398 & R399, green) is accessible and free to interact with the SNAREs. However, the occupancy and orientation of the SNAREs on the Syt1 ring is not known.