Figure 4.

Overview of mutations in STX3 and STXBP2. A: The syntaxin‐3 protein with known domains and locations of STX3 mutations. B: Overview of the munc18‐2 protein with known domains and locations of STXBP2 mutations associated with chronic diarrhea in patients. C: A homology model of syntaxin‐3‐munc18‐2 complex based on syntaxin‐1/munc18‐1 and munc18‐2 crystal structures (PDB ID 4JEU, 4CCA). In closed conformation of syntaxin‐3 regulatory Habc domain (composed of three helixes a, b, c) interacts with H3 domain containing a SNARE motif. Munc18‐2 domains 1 (dom 1) and 3 create a main syntaxin‐3‐binding surface. Syntaxin‐3 N‐terminal peptide binds to the opposite surface of the domain 1. Residues affected by MVID related mutations are shown in spheres and labeled. D: Overview of the munc18‐2 protein with known domains and locations of STXBP2 mutations associated with absence of chronic diarrhea in patients. Mutations indicted in black, red, gray, and blue represent missense, frameshift/nonsense, splicing, and deletions, respectively