Fig. 2.

Structure of the protein system at the pre-fusion stage of a vesicle in BBB. (a) The zoomed-in view of key components: Vesicular membrane, endothelial cell membrane in the brain side, and associate proteins involved in the pre-fusion stage. Protein complex involves in this process includes VAMP8 (orange), Complexin (pink), Syntaxin2 (gray), and SNAP23 (blue), and Slp4-a (green). (b) The new cartoon model for Slp4-a (cyan-colored), which consists of C2A and C2B domains. Each C2 domain shows both the Ca²⁺ binding site and additional binding sites with some important amino acids. Calcium ions (yellow) are shown in the calcium binding site. The additional binding site is located on the opposite side of the Ca²⁺ binding site in each domain. Lipids are shown as gray layers located at the top and bottom sides of the Slp4-a. (c) Sketch of the Slp4-a model with four important regions: two Ca²⁺ binding sites in green and two additional binding regions in blue. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)