Correlation Engine 2.0
Clear Search sequence regions


  • C2A (2)
  • C2B (2)
  • Ca2 (2)
  • calcium (2)
  • lipid (2)
  • NMR (1)
  • phospholipid (1)
  • Synaptotagmin I (2)
  • synaptotagmins (2)
  • Syt1 (5)
  • Sizes of these terms reflect their relevance to your search.

    Synaptotagmin 1 (Syt1) is an integral membrane protein whose phospholipid-binding tandem C2 domains, C2A and C2B, act as Ca2+ sensors of neurotransmitter release. Our objective was to understand the role of individual metal-ion binding sites of these domains in the membrane association process. We used Pb2+, a structural and functional surrogate of Ca2+, to generate the protein states with well-defined protein-metal ion stoichiometry. NMR experiments revealed that binding of one divalent metal ion per C2 domain results in loss of conformational plasticity of the loop regions, potentially pre-organizing them for additional metal-ion and membrane-binding events. In C2A, a divalent metal ion in site 1 is sufficient to drive its weak association with phosphatidylserine-containing membranes, whereas in C2B, it enhances the interactions with the signaling lipid phosphatidylinositol-4,5-bisphosphate. In full-length Syt1, both Pb2+-complexed C2 domains associate with phosphatidylserine-containing membranes. Electron paramagnetic resonance experiments show that the extent of membrane insertion correlates with the occupancy of the C2 metal ion sites. Together, our results indicate that upon partial metal ion saturation of the intra-loop region, Syt1 adopts a dynamic, partially membrane-bound state. The properties of this state, such as conformationally restricted loop regions and positioning of C2 domains in close proximity to anionic lipid headgroups, "prime" Syt1 for cooperative binding of a full complement of metal ions and deeper membrane insertion. Copyright © 2020 Biophysical Society. Published by Elsevier Inc. All rights reserved.

    Citation

    Sachin Katti, Sarah B Nyenhuis, Bin Her, David S Cafiso, Tatyana I Igumenova. Partial Metal Ion Saturation of C2 Domains Primes Synaptotagmin 1-Membrane Interactions. Biophysical journal. 2020 Mar 24;118(6):1409-1423

    Expand section icon Mesh Tags

    Expand section icon Substances


    PMID: 32075747

    View Full Text