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, Josep Rizo

Research output: Contribution to journalArticle

270 Citations (Scopus)

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
Externally publishedYes

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Synaptotagmin I
Neurotransmitter Agents
Phospholipids
Synaptotagmins
Ions
C2 Domains

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Fernandez, I., Araç, D., Ubach, J., Gerber, S. H., Shin, O. H., Gao, Y., ... Rizo, 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

Three-dimensional structure of the synaptotagmin 1 C2B-domain : Synaptotagmin 1 as a phospholipid binding machine. / Fernandez, Imma; Araç, Demet; Ubach, Josep; Gerber, Stefan H.; Shin, Ok Ho; Gao, Yan; Anderson, Richard G W; Südhof, Thomas C.; Rizo, Josep.

In: Neuron, Vol. 32, No. 6, 20.12.2001, p. 1057-1069.

Research output: Contribution to journalArticle

Fernandez, I, Araç, D, Ubach, J, Gerber, SH, Shin, OH, Gao, Y, Anderson, RGW, Südhof, TC & Rizo, J 2001, 'Three-dimensional structure of the synaptotagmin 1 C2B-domain: Synaptotagmin 1 as a phospholipid binding machine', Neuron, vol. 32, no. 6, pp. 1057-1069. https://doi.org/10.1016/S0896-6273(01)00548-7
Fernandez, Imma ; Araç, Demet ; Ubach, Josep ; Gerber, Stefan H. ; Shin, Ok Ho ; Gao, Yan ; Anderson, Richard G W ; Südhof, Thomas C. ; Rizo, Josep. / Three-dimensional structure of the synaptotagmin 1 C2B-domain : Synaptotagmin 1 as a phospholipid binding machine. In: Neuron. 2001 ; Vol. 32, No. 6. pp. 1057-1069.
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