Document Detail

Structure of alpha-latrotoxin oligomers reveals that divalent cation-dependent tetramers form membrane pores.
MedLine Citation:
PMID:  10625427     Owner:  NLM     Status:  MEDLINE    
We report here the first three-dimensional structure of alpha-latrotoxin, a black widow spider neurotoxin, which forms membrane pores and stimulates secretion in the presence of divalent cations. We discovered that alpha-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 A and 14 A resolution, respectively, using cryo-electron microscopy and angular reconstitution. The alpha-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 alpha-latrotoxin; they have an axial channel and can insert into lipid bilayers with their hydrophobic base, providing the first model of alpha-latrotoxin pore formation.
E V Orlova; M A Rahman; B Gowen; K E Volynski; A C Ashton; C Manser; M van Heel; Y A Ushkaryov
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Nature structural biology     Volume:  7     ISSN:  1072-8368     ISO Abbreviation:  Nat. Struct. Biol.     Publication Date:  2000 Jan 
Date Detail:
Created Date:  2000-01-18     Completed Date:  2000-01-18     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421566     Medline TA:  Nat Struct Biol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  48-53     Citation Subset:  IM    
Biochemistry Department, Imperial College, Exhibition Road, London SW7 2AY, UK.
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MeSH Terms
Amino Acid Sequence
Black Widow Spider / chemistry*
Calcium / pharmacology
Cations, Divalent / pharmacology*
Cryoelectron Microscopy
Edetic Acid / pharmacology
Magnesium / pharmacology
Membrane Proteins / chemistry*,  ultrastructure*
Models, Molecular
Molecular Sequence Data
Molecular Weight
Norepinephrine / metabolism
Presynaptic Terminals / drug effects,  metabolism
Protein Denaturation
Protein Renaturation / drug effects
Protein Structure, Quaternary / drug effects*
Protein Structure, Tertiary
Sequence Alignment
Spider Venoms / chemistry*,  pharmacology
Structure-Activity Relationship
Reg. No./Substance:
0/Cations, Divalent; 0/Membrane Proteins; 0/Spider Venoms; 51-41-2/Norepinephrine; 60-00-4/Edetic Acid; 65988-34-3/alpha-latrotoxin; 7439-95-4/Magnesium; 7440-70-2/Calcium
Comment In:
Nat Struct Biol. 2000 Jan;7(1):3-4   [PMID:  10625413 ]

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