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| Title | Symmetrical organization of proteins under docked synaptic vesicles. |
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| Journal, issue, pages | FEBS Lett, Vol. 593, Issue 2, Page 144-153, Year 2019 |
| Publish date | Jan 18, 2019 |
Authors | Xia Li / Abhijith Radhakrishnan / Kirill Grushin / Ravikiran Kasula / Arunima Chaudhuri / Sujatha Gomathinayagam / Shyam S Krishnakumar / Jun Liu / James E Rothman / ![]() |
| PubMed Abstract | During calcium-regulated exocytosis, the constitutive fusion machinery is 'clamped' in a partially assembled state until synchronously released by calcium. The protein machinery involved in this ...During calcium-regulated exocytosis, the constitutive fusion machinery is 'clamped' in a partially assembled state until synchronously released by calcium. The protein machinery involved in this process is known, but the supra-molecular architecture and underlying mechanisms are unclear. Here, we use cryo-electron tomography analysis in nerve growth factor-differentiated neuro-endocrine (PC12) cells to delineate the organization of the release machinery under the docked vesicles. We find that exactly six exocytosis modules, each likely consisting of a single SNAREpin with its bound Synaptotagmins, Complexin, and Munc18 proteins, are symmetrically arranged at the vesicle-PM interface. Mutational analysis suggests that the symmetrical organization is templated by circular oligomers of Synaptotagmin. The observed arrangement, including its precise radial positioning, is in-line with the recently proposed 'buttressed ring hypothesis'. |
External links | FEBS Lett / PubMed:30561792 / PubMed Central |
| Methods | EM (subtomogram averaging) |
| Resolution | 50.0 Å |
| Structure data | ![]() EMDB-0413: ![]() EMDB-0414: |
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