Structure of α-latrotoxin oligomers reveals that divalent cation- dependent tetramers form membrane pores

被引:114
作者
Orlova E.V. [1 ]
Atiqur Rahman M. [1 ]
Gowen B. [1 ]
Volynski K.E. [1 ]
Ashton A.C. [1 ]
Manser C. [1 ]
Van Heel M. [1 ]
Ushkaryov Y.A. [1 ]
机构
[1] Biochemistry Department, Imperial College, London SW7 2AY, Exhibition Road
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
D O I
10.1038/71247
中图分类号
学科分类号
摘要
We report here the first three-dimensional structure of α-latrotoxin, a black widow spider neurotoxin, which forms membrane pores and stimulates secretion in the presence of divalent cations. We discovered that α- 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 α-latrotoxin monomer consists of three domains. The N- and C-terminal domains have been identified using antibodies and atomic fitting. The CA- symmetric tetramers represent the active form of α-latrotoxin; they have an axial channel and can insert into lipid bilayers with their hydrophobic base, providing the first model of α-latrotoxin pore formation.
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页码:48 / 53
页数:5
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