Homotetrameric structure of the SNAP-23 N-terminal coiled-coil domain

J Biol Chem. 2003 Apr 11;278(15):13462-7. doi: 10.1074/jbc.M210483200. Epub 2003 Jan 29.


SNARE proteins mediate intracellular membrane fusion by forming a coiled-coil complex to merge opposing membranes. A "fusion-active" neuronal SNARE complex is a parallel four-helix bundle containing two coiled-coil domains from SNAP-25 and one coiled-coil domain each from syntaxin-1a and VAMP-2. "Prefusion" assembly intermediate complexes can also form from these SNAREs. We studied the N-terminal coiled-coil domain of SNAP-23 (SNAP-23N), a non-neuronal homologue of SNAP-25, and its interaction with other coiled-coil domains. SNAP-23N can assemble spontaneously with the coiled-coil domains from SNAP-23C, syntaxin-4, and VAMP-3 to form a heterotetrameric complex. Unexpectedly, pure SNAP-23N crystallizes as a coiled-coil homotetrameric complex. The four helices have a parallel orientation and are symmetrical about the long axis. The complex is stabilized through the interaction of conserved hydrophobic residues comprising the a and d positions of the coiled-coil heptad repeats. In addition, a central, highly conserved glutamine residue (Gln-48) is buried within the interface by hydrogen bonding between glutamine side chains derived from adjacent subunits and to solvent molecules. A comparison of the SNAP-23N structure to other SNARE complex structures reveals how a simple coiled-coil motif can form diverse SNARE complexes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / ultrastructure
  • Crystallography, X-Ray
  • Humans
  • Macromolecular Substances
  • Models, Molecular
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Protein Conformation
  • Protein Structure, Secondary
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Recombinant Proteins / chemistry
  • Sequence Alignment
  • Sequence Homology, Amino Acid


  • Carrier Proteins
  • Macromolecular Substances
  • Qb-SNARE Proteins
  • Qc-SNARE Proteins
  • Recombinant Proteins
  • SNAP23 protein, human

Associated data

  • PDB/1NHL

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