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 language | English (US) |
|---|---|
| Pages (from-to) | 1057-1069 |
| Number of pages | 13 |
| Journal | Neuron |
| Volume | 32 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 20 2001 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Neuroscience(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Three-dimensional structure of the synaptotagmin 1 C2B-domain
T2 - Synaptotagmin 1 as a phospholipid binding machine
AU - Fernandez, Imma
AU - Araç, Demet
AU - Ubach, Josep
AU - Gerber, Stefan H.
AU - Shin, Ok Ho
AU - Gao, Yan
AU - Anderson, Richard G W
AU - Südhof, Thomas C.
AU - Rizo, Josep
PY - 2001/12/20
Y1 - 2001/12/20
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0035924571&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(01)00548-7
DO - 10.1016/S0896-6273(01)00548-7
M3 - Article
C2 - 11754837
AN - SCOPUS:0035924571
VL - 32
SP - 1057
EP - 1069
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 6
ER -