The X-ray crystal structure of neuronal Sec1 from squid sheds new light on the role of this protein in exocytosis

Structure. 2000 Jul 15;8(7):685-94. doi: 10.1016/s0969-2126(00)00156-8.


Background: Sec1-like molecules have been implicated in a variety of eukaryotic vesicle transport processes including neurotransmitter release by exocytosis. They regulate vesicle transport by binding to a t-SNARE from the syntaxin family. This process is thought to prevent SNARE complex formation, a protein complex required for membrane fusion. Whereas Sec1 molecules are essential for neurotransmitter release and other secretory events, their interaction with syntaxin molecules seems to represent a negative regulatory step in secretion.

Results: Here we report the X-ray crystal structure of a neuronal Sec1 homologue from squid, s-Sec1, at 2.4 A resolution. Neuronal s-Sec1 is a modular protein that folds into a V-shaped three-domain assembly. Peptide and mutagenesis studies are discussed with respect to the mechanism of Sec1 regulation. Comparison of the structure of squid s-Sec1 with the previously determined structure of rat neuronal Sec1 (n-Sec1) bound to syntaxin-1a indicates conformational rearrangements in domain III induced by syntaxin binding.

Conclusions: The crystal structure of s-Sec1 provides the molecular scaffold for a number of molecular interactions that have been reported to affect Sec1 function. The structural differences observed between s-Sec1 and the structure of a rat n-Sec1-syntaxin-1a complex suggest that local conformational changes are sufficient to release syntaxin-1a from neuronal Sec1, an active process that is thought to involve additional effector molecule(s).

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Amino Acids / chemistry
  • Animals
  • Antigens, Surface / metabolism
  • Crystallography, X-Ray
  • Decapodiformes / chemistry*
  • Exocytosis*
  • Membrane Fusion
  • Membrane Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Munc18 Proteins
  • Mutagenesis, Site-Directed
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology
  • Phosphorylation
  • Protein Conformation
  • Protein Folding
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • Rats
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • SNARE Proteins
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Species Specificity
  • Structure-Activity Relationship
  • Synaptic Vesicles / metabolism
  • Syntaxin 1
  • Vesicular Transport Proteins*


  • Amino Acids
  • Antigens, Surface
  • Membrane Proteins
  • Munc18 Proteins
  • Nerve Tissue Proteins
  • Recombinant Fusion Proteins
  • SNARE Proteins
  • Stx1a protein, rat
  • Syntaxin 1
  • Vesicular Transport Proteins

Associated data

  • PDB/1EPU