The longin SNARE VAMP7/TI-VAMP adopts a closed conformation

J Biol Chem. 2010 Jun 4;285(23):17965-73. doi: 10.1074/jbc.M110.120972. Epub 2010 Apr 8.

Abstract

SNARE protein complexes are key mediators of exocytosis by juxtaposing opposing membranes, leading to membrane fusion. SNAREs generally consist of one or two core domains that can form a four-helix bundle with other SNARE core domains. Some SNAREs, such as syntaxin target-SNAREs and longin vesicular-SNAREs, have independent, folded N-terminal domains that can interact with their respective SNARE core domains and thereby affect the kinetics of SNARE complex formation. This autoinhibition mechanism is believed to regulate the role of the longin VAMP7/TI-VAMP in neuronal morphogenesis. Here we use nuclear magnetic resonance spectroscopy to study the longin-SNARE core domain interaction for VAMP7. Using complete backbone resonance assignments, chemical shift perturbations analysis, and hydrogen/deuterium exchange experiments, we conclusively show that VAMP7 adopts a preferentially closed conformation in solution. Taken together, the closed conformation of longins is conserved, in contrast to the syntaxin family of SNAREs for which mixtures of open and closed states have been observed. This may indicate different regulatory mechanisms for SNARE complexes containing syntaxins and longins, respectively.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA, Complementary / metabolism
  • Humans
  • Light
  • Magnetic Resonance Spectroscopy / methods
  • Models, Molecular
  • Molecular Conformation
  • Neurons / metabolism
  • Protein Conformation
  • Protein Structure, Tertiary
  • Qa-SNARE Proteins / chemistry
  • R-SNARE Proteins / chemistry*
  • SNARE Proteins / chemistry*

Substances

  • DNA, Complementary
  • Qa-SNARE Proteins
  • R-SNARE Proteins
  • SNARE Proteins
  • VAMP7 protein, human