Fig 2: The Juxtamembrane Motif of the v-SNARE Is Embedded in the Surface of the Lipid Bilayer(A) Sequence alignment of the juxtamembrane motifs (highlighted in yellow) of exocytic v-SNAREs from multiple species. The SNARE motif is also known as the core domain. TMD, transmembrane domain.(B) Model of the VAMP2 juxtamembrane motif embedded in a membrane bilayer. Magenta, VAMP2 (v-SNARE, the juxtamembrane motif is highlighted in yellow); green, syntaxin-1 (t-SNARE); blue, SNAP-25 (t-SNARE, only the SNARE motifs are shown); orange, Munc18-1 (SM protein, shown as a surface model). The juxtamembrane motif of VAMP2 is based on previous biophysical and structural data (Bowen and Brunger, 2006; Brewer et al., 2011; Ellena et al., 2009; Kweon et al., 2003). The TMD of VAMP2 is tilted about 35° relative to the membrane normal to allow the nonpolar residues of the juxtamembrane motif to insert into the hydrophobic phase of the bilayer and the basic residues to embed in the hydrophilic phase of the membrane. Carbon, oxygen, and phosphorus atoms of the lipid bilayer are colored gray, red, and green, respectively. The model is based on the structures of the v-SNARE (PDB: 2KOG; Ellena et al., 2009), the cis-SNARE complex (PDB: 3HD7; Stein et al., 2009), and Munc18-1 (PDB: 3PUJ; Hu et al., 2011). Because the structure of Munc18-1 bound to the half-zippered trans-SNARE complex has not been determined, the position of Munc18-1 depicted in the model is arbitrary. The model of the phosphatidylcholine bilayer (popc128a.pdb) was obtained from the Department of Biocomputing at the University of Calgary (Calgary, AB, Canada). The models were prepared using PyMOL (DeLano Scientific LLC, San Carlos, CA).