Duyoung Min1,2,*, Kipom Kim2,*, Changbong Hyeon3, Yong Hoon Cho2, Yeon-Kyun Shin4,5 & Tae-Young Yoon1,2
1 National Creative Research Initiative Center for Single-Molecule Systems Biology, KAIST, Daejeon 305-701, South Korea. 2 Department of Physics, KAIST, Daejeon 305-701, South Korea. 3 School of Computational Sciences, Korea Institute for Advanced Study, Seoul 130-722, South Korea. 4 Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 136-791, South Korea. 5 Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, Iowa 50011, USA. * These authors contributed equally to this work.
Correspondence to: Tae-Young Yoon or Yeon-Kyun Shin
Formation of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex provides mechanical thrust for membrane fusion, but its molecular mechanism is still unclear. Here using magnetic tweezers, we observe mechanical responses of a single neuronal SNARE complex under constant pulling force. Single SNARE complexes may be unzipped with 34pN force. When rezipping is induced by lowering the force to 11pN, only a partially assembled state results, with the C-terminal half of the SNARE complex remaining disassembled. Reassembly of the C-terminal half occurs only when the force is further lowered below 11pN. Thus, mechanical hysteresis, characterized by the unzipping and rezipping cycle of a single SNARE complex, produces the partially assembled state. In this metastable state, unzipping toward the N-terminus is suppressed while zippering toward the C-terminus is initiated as a steep function of force. This ensures the directionality of SNARE-complex formation, making the SNARE complex a robust force-generating machine.