The N-terminal interaction of Munc18-1 and Sx1a. A, the Munc18-1-Sx1a complex represented as ribbon (left) and surface (right) models with the two key binding sites indicated. These involve the Sx1a N-terminal peptide (residues 2–9), and the combined Sx1a Habc and H3 domains (residues 26–248). B, key residues required for forming the SM protein/N-peptide interaction in the Munc18c:Sx4-(1–29) crystal structure (top, PDB code 2PJX) (16) are present in the Munc18-1:Sx1a model (middle) and the newly refined Munc18-1:Sx1a structure (bottom, PDB code 3C98)(20). Conserved hydrophobic residues defining the pocket are shown (blue). C, sequences of Syntaxin1a (Homo sapiens, Rattus norvegicus, and Mus musculus), Syntaxin4 (H. sapiens, R. norvegicus, and M. musculus), and Sed5p (S. cerevisiae) N termini were aligned. Conserved residues are highlighted (orange).