Conservation of SNARE complex structure. (A) Sequence variation (black line) for selected syntaxin (SX), synaptobrevin (SB), and SNAP-25 (residues 27–82, SN1; residues 148–203, SN2) families and surface accessibilities (gray bars) in the synaptic fusion complex crystal structure. The analysis was restricted to the 16 layers (indicated by arrowheads) of the synaptic fusion complex crystal structure (5) consisting of syntaxin-1A residues 201–255 (SX), SNAP-25B residues 28–82 (SN1) and residues 149–203 (SN2), and synaptobrevin residues 31–85 (SB). The layer numbers refer to Fig. 1B. The GenBank accession numbers used for the syntaxin-1 through -4 family are as follows: sx-1b, RN, P32853; sx1b, BS, P41414; sx-1a, RN, P32851; sx-1a, HS, L37792; sx-1a, MM, D45208; sx-A, HS, U12918; sx1a, BS, P32850; sx1, HM, U85807; sx, AC, U03123; sx1a, DM, L37732; unc-64b, CE, AF047885; sx, SP, AF014122; sx2, RN, P50279; sx3, RN, Q08849; sx3a, HS, AJ002076; sx4, RN, Q08850; sx4, HS, X85784; and sx4, MM, U76832. The accession numbers used for the SNAP-25 family are SNAP-25B, HS, P13795; SNAP-25, TM, P36976; syndet, MM, U73143; SNAP-25, SP, AF036902; SNAP-25, DM, U81153; SNAP-25, HM, U85806; SNAP-25, GG, L09253; SNAP-25A, CA, L22973; SNAP-25D, CA, L22976; and Y22F5A.5, CE, AL021479. The accession numbers used for the synaptobrevin family members in the second branch of the dendrogram (not shown) are Sb1, RN, M24104; Sb1B, RN, U74621; Sb1, MM, AF007167; Sb1, TM, P13701; Syb-B, DM, L14270; Syb-A, DM, L14270; N-Syb, DM, S66686; Sb, AC, P35589; cellubrevin (Sb3), MM U61751; cellubrevin (Sb3), RN S63830; Sb, SP, AF014119; Sb2, RN, M24105; Sb2, HS, AJ5044; Sb2, MM, AF007168; Sb, HM, U85805; Sb, FR, AF016494; Sb, LP, X74748; XSybI, XL, AF035016; Syb2, XL, U16801; Sb, BT, X76199; Snb1, CE, AF003281; and Sb, SM, U30182. The following two-letter species abbreviations are used: CA, Carrassius auratus; HS, Homo sapiens; MM, Mus musculus; RN, Rattus norvegicus; SC, Saccharomyces cerevisiae; DM, Drosophila melanogaster; TM, Torpedo marmorata; CE, Caenorhabditis elegans; SP, Strongylocentrotus purpuratus; HM, Hirudo medicinalis; GG, Gallus gallus; BT, Bos taurus; AC, Aplysia californica; SM, Schistosoma mansoni; FR, Fugu rubripes; XL, Xenopus laevis; and LP, Loligo pealei. (B) Model of a synaptic fusion complex consisting of syntaxin-4, SNAP-25B, and synaptobrevin-II, based on the crystal structure of the synaptic fusion complex (5), which contains syntaxin-1A. Syntaxin-4 residues are shown in black and red for matching and different residue types between syntaxin-1A and syntaxin-4, respectively. Most substituted residues occur on the surface of the complex.