Yoosoo Yanga,1, Jae Yoon Shina,1, Jung-Mi Oha, Chang Hwa Junga, Yunha Hwanga, Sehyun Kima, Jun-Seob Kima, Kee-Jung Yoona, Ji-Young Ryub, Jaeil Shinc, Jae Sung Hwangd, Tae-Young Yoonb, Yeon-Kyun Shinc,e,2, and Dae-Hyuk Kweona,2
aSchool of Life Science and Biotechnology and Center for Human Interface Nanotechnology, Sungkyunkwan University, Suwon 440-746, South Korea;
bDepartment of Physics, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 760-749, South Korea;
cDepartment of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011;
dSkin Biotechnology Center, Graduate School of Biotechnology and Institute of Life Science and Resources, Kyung Hee University, Yongin 446-701, Korea; and
eIntegrative Biology and Biotechnology, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Korea
Edited by Josep Rizo, University of Texas Southwestern Medical Center, Dallas, TX, and accepted by the Editorial Board November 8, 2010 (received for review May 18, 2010)
1Y.Y. and J.Y.S. contributed equally to this work.
Neuronal SNARE proteins mediate neurotransmitter release at the synapse by facilitating the fusion of vesicles to the presynaptic plasma membrane. Cognate v-SNAREs and t-SNAREs from the vesicle and the plasma membrane, respectively, zip up and bring about the apposition of two membranes attached at the C-terminal ends. Here, we demonstrate that SNARE zippering can be modulated in the midways by wedging with small hydrophobic molecules. Myricetin, which intercalated into the hydrophobic inner core near the middle of the SNARE complex, stopped SNARE zippering in motion and accumulated the trans-complex, where the N-terminal region of v-SNARE VAMP2 is in the coiled coil with the frayed C-terminal region. Delphinidin and cyanidin inhibited N-terminal nucleation of SNARE zippering. Neuronal SNARE complex in PC12 cells showed the same pattern of vulnerability to small hydrophobic molecules. We propose that the half-zipped trans-SNARE complex is a crucial intermediate waiting for a calcium trigger that leads to fusion pore opening.
polyphenol, hemifusion, neurotransmission, neuron
2To whom correspondence may be addressed.
Author contributions: Y.Y., T.-Y.Y., Y.-K.S., and D.-H.K. designed research; Y.Y., J.Y.S., J.-M.O., C.H.J., Y.H., S.K., J.-S.K., J.-Y.R., and J.S. performed research; J.Y.S., C.H.J., K.-J.Y., J.-Y.R., and J.S.H. contributed new reagents/analytic tools; Y.Y., Y.-K.S., and D.-H.K. analyzed data; and T.-Y.Y., Y.-K.S., and D.-H.K. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. J.R. is a guest editor invited by the Editorial Board.
This article contains supporting information online at