Figure 6. Model of Syt7 C2A membrane docking mechanism.

A: Proposed two-step docking model. In step 1, C2 domains interact with Ca²⁺ ions (orange circles) to drive initial electrostatic docking to membranes containing anionic lipid headgroups (red circles). Both Syt1 C2A (red box) and Syt7 C2A (blue box, inclusive of both steps) can participate in this docking event. In this model, Syt7 C2A but not Syt1 C2A can also undergo a transition to a more deeply inserted docking geometry (step 2). B: Membrane docking geometry for Syt1 C2A previously determined through electron paramagnetic resonance (EPR) depth measurements (13). The published solution structure of Ca²⁺-bound Syt1 C2A (PDB ID 1BYN (62)) is drawn aligned to the membrane in an illustration of the EPR-determined geometry reported by Frazier, et al. (13). The amino acid sidechains of Phe234 and Met173 on the membrane-inserted Ca²⁺ binding loops are shown (green sticks). C: Hypothesized membrane docking geometry of Syt7 C2A. The solution structure of Syt7 C2A (PDB ID 2D8K) is drawn aligned to the membrane in a manner allowing penetration of both Phe229 and Phe167 (green sticks) into the hydrocarbon interior of the membrane. For clarity in illustration, three Ca²⁺ ions were modeled into the Ca²⁺-free 2D8K structure based on their position in 1BYN after backbone alignment of the two structures. Panels B and C were created using MacPyMol.