5VFE
Synaptotagmin 1 C2A domain, lead-bound
Summary for 5VFE
| Entry DOI | 10.2210/pdb5vfe/pdb |
| Related | 5VFF 5VFG |
| Descriptor | Synaptotagmin-1, LEAD (II) ION, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | metal binding protein, c2a domain |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 2 |
| Total formula weight | 29657.70 |
| Authors | Taylor, A.B.,Hart, P.J.,Igumenova, T.I. (deposition date: 2017-04-07, release date: 2018-04-11, Last modification date: 2023-10-04) |
| Primary citation | 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 Cited by 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: 30063057DOI: 10.1039/c8mt00135a PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.38 Å) |
Structure validation
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