Enlightening molecular mechanisms through study of protein interactions

Jose Rizo-Rey, Michael K Rosen, Kevin H Gardner

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


The investigation of molecular mechanisms is a fascinating area of current biological research that unites efforts from scientists with very diverse expertise. This review provides a perspective on the characterization of protein interactions as a central aspect of this research. We discuss case studies on the neurotransmitter release machinery that illustrate a variety of principles and emphasize the power of combining nuclear magnetic resonance (NMR) spectroscopy with other biophysical techniques, particularly X-ray crystallography. These studies have shown that: (i) the soluble SNAP receptor (SNARE) proteins form a tight complex that brings the synaptic vesicle and plasma membranes together, which is key for membrane fusion; (ii) the SNARE syntaxin-1 adopts an autoinhibitory closed conformation; (iii) Munc18-1 plays crucial functions through interactions with closed syntaxin-1 and with the SNARE complex; (iv) Munc13s mediate the opening of syntaxin-1; (v) complexins play dual roles through distinct interactions with the SNARE complex; (vi) synaptotagmin-1 acts a Ca2 sensor, interacting simultaneously with the membranes and the SNAREs; and (vii) a Munc13 homodimer to Munc13-RIM heterodimer switch modulates neurotransmitter release. Overall, this research underlines the complexities involved in elucidating molecular mechanisms and how these mechanisms can depend critically on an interplay between strong and weak protein interactions.

Original languageEnglish (US)
Pages (from-to)270-283
Number of pages14
JournalJournal of molecular cell biology
Issue number5
StatePublished - Oct 2012


  • NMR spectroscopy
  • X-ray crystallography
  • membrane fusion
  • molecular mechanisms
  • neurotransmitter release
  • protein interactions

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology


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