We report here the first three-dimensional structure of -latrotoxin,
a black widow spider neurotoxin, which forms membrane pores and stimulates
secretion in the presence of divalent cations. We discovered that -latrotoxin
exists in two oligomeric forms: it is dimeric in EDTA but forms tetramers
in the presence of Ca2+ or Mg2+. The dimer and
tetramer structures were determined independently at 18 Å and 14 Å
resolution, respectively, using cryo-electron microscopy and angular reconstitution.
The -latrotoxin monomer consists of three domains. The N- and C-terminal
domains have been identified using antibodies and atomic fitting. The C4-symmetric
tetramers represent the active form of -latrotoxin; they have an axial
channel and can insert into lipid bilayers with their hydrophobic base, providing
the first model of -latrotoxin pore formation.
-latrotoxin oligomers reveals that divalent cation-dependent
tetramers form membrane pores
-latrotoxin,
a black widow spider neurotoxin, which forms membrane pores and stimulates
secretion in the presence of divalent cations. We discovered that 
