5VFF

Synaptotagmin 1 C2B domain, lead-bound (low occupancy)

5VFF の概要

• エントリーDOI: 10.2210/pdb5vff/pdb
• 関連するPDBエントリー: 5VFE 5VFG
• 分子名称: Synaptotagmin-1, LEAD (II) ION (3 entities in total)
• 機能のキーワード: metal binding protein, c2b domain
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 17415.21

構造登録者

Taylor, A.B.,Hart, P.J.,Igumenova, T.I. (登録日: 2017-04-07, 公開日: 2018-04-11, 最終更新日: 2023-10-04)

主引用文献

Katti, S.,Her, B.,Srivastava, A.K.,Taylor, A.B.,Lockless, S.W.,Igumenova, T.I.
High affinity interactions of Pb2+with synaptotagmin I.
Metallomics, 10:1211-1222, 2018

PubMed Abstract: Lead (Pb) is a potent neurotoxin that disrupts synaptic neurotransmission. We report that Synaptotagmin I (SytI), a key regulator of Ca2+-evoked neurotransmitter release, has two high-affinity Pb2+ binding sites that belong to its cytosolic C2A and C2B domains. The crystal structures of Pb2+-complexed C2 domains revealed that protein-bound Pb2+ ions have holodirected coordination geometries and all-oxygen coordination spheres. The on-rate constants of Pb2+ binding to the C2 domains of SytI are comparable to those of Ca2+ and are diffusion-limited. In contrast, the off-rate constants are at least two orders of magnitude smaller, indicating that Pb2+ can serve as both a thermodynamic and kinetic trap for the C2 domains. We demonstrate, using NMR spectroscopy, that population of these sites by Pb2+ ions inhibits further Ca2+ binding despite the existing coordination vacancies. Our work offers a unique insight into the bioinorganic chemistry of Pb(ii) and suggests a mechanism by which low concentrations of Pb2+ ions can interfere with the Ca2+-dependent function of SytI in the cell.

PubMed: 30063057
DOI: 10.1039/c8mt00135a

実験手法

X-RAY DIFFRACTION (1.413 Å)