Inferring synaptotagmin function from C2 domain stability: Analysis of structurally defined mutations in synaptotagmin 1 C2A
Poster Jan 28, 2008
Synaptotagmin 1 (Syt1) triggers the release of neurotransmitter from docked synaptic vesicles through its interactions with Ca+2, phospholipid and the SNARE complex. We tested whether the disruption of this single H-bond can affect the shape of the Ca+2 binding pocket of C2A by causing loop 3 to collapse.
These results support the use of hSC-CM and MEA technology for preclinical assessment of proarrhythmic risk within the proposed CiPA paradigm, and, more generally, demonstrate that automation of the CM-MEA assay can achieve high reliability and throughput for cardiac risk assessment in vitro.READ MORE