Phospholipids Differentially Regulate Ca²⁺ Binding to Synaptotagmin-1.

ABSTRACT: Synaptotagmin-1 (Syt-1) is a calcium sensing protein that is resident in synaptic vesicles. It is well established that Syt-1 is essential for fast and synchronous neurotransmitter release. However, the role of Ca²⁺ and phospholipid binding in the function of Syt-1, and ultimately in neurotransmitter release, is unclear. Here, we investigate the binding of Ca²⁺ to Syt-1, first in the absence of lipids, using native mass spectrometry to evaluate individual binding affinities. Syt-1 binds to one Ca²⁺ with a K_D ∼ 45 μM. Each subsequent binding affinity (n ≥ 2) is successively unfavorable. Given that Syt-1 has been reported to bind anionic phospholipids to modulate the Ca²⁺ binding affinity, we explored the extent that Ca

SUBMITTER: Lawrence SAS 

PROVIDER: S-EPMC11040605 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature