Three-dimensional structure of the synaptotagmin 1 C2B-domain: Synaptotagmin 1 as a phospholipid binding machine

Imma Fernandez, Demet Araç, Josep Ubach, Stefan H. Gerber, Ok Ho Shin, Yan Gao, Richard G W Anderson, Thomas C. Südhof, Jose Rizo-Rey

Research output: Contribution to journalArticle

278 Scopus citations

Abstract

Synaptotagmin 1 probably functions as a Ca2+ sensor in neurotransmitter release via its two C2-domains, but no common Ca2+-dependent activity that could underlie a cooperative action between them has been described. The NMR structure of the C2B-domain now reveals a β sandwich that exhibits striking similarities and differences with the C2A-domain. Whereas the bottom face of the C2B-domain has two additional α helices that may be involved in specialized Ca2+-independent functions, the top face binds two Ca2+ ions and is remarkably similar to the C2A-domain. Consistent with these results, but in contrast to previous studies, we find that the C2B-domain binds phospholipids in a Ca2+-dependent manner similarly to the C2A-domain. These results suggest a novel view of synaptotagmin function whereby the two C2-domains cooperate in a common activity, Ca2+-dependent phospholipid binding, to trigger neurotransmitter release.

Original languageEnglish (US)
Pages (from-to)1057-1069
Number of pages13
JournalNeuron
Volume32
Issue number6
DOIs
StatePublished - Dec 20 2001

ASJC Scopus subject areas

  • Neuroscience(all)

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    Fernandez, I., Araç, D., Ubach, J., Gerber, S. H., Shin, O. H., Gao, Y., Anderson, R. G. W., Südhof, T. C., & Rizo-Rey, J. (2001). Three-dimensional structure of the synaptotagmin 1 C2B-domain: Synaptotagmin 1 as a phospholipid binding machine. Neuron, 32(6), 1057-1069. https://doi.org/10.1016/S0896-6273(01)00548-7