Rxivist logo

Rxivist combines preprints from bioRxiv with data from Twitter to help you find the papers being discussed in your field. Currently indexing 70,429 bioRxiv papers from 307,558 authors.

High affinity interactions of Pb2+ with Synaptotagmin I

By Sachin Katti, Bin Her, Atul K Srivastava, Alexander B. Taylor, Steve W Lockless, Tatyana I. Igumenova

Posted 16 Jun 2018
bioRxiv DOI: 10.1101/348748 (published DOI: 10.1039/c8mt00135a)

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 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.

Download data

  • Downloaded 161 times
  • Download rankings, all-time:
    • Site-wide: 57,277 out of 70,410
    • In biophysics: 2,480 out of 2,999
  • Year to date:
    • Site-wide: 67,818 out of 70,410
  • Since beginning of last month:
    • Site-wide: 58,503 out of 70,410

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)