7T7V
Munc13-1 C1-C2B-MUN-C2C Lateral conformation on lipid bilayer surface
Summary for 7T7V
| Entry DOI | 10.2210/pdb7t7v/pdb |
| Related | 7T7C |
| EMDB information | 25737 25739 |
| Descriptor | Protein unc-13 homolog A (1 entity in total) |
| Functional Keywords | synaptic transmission, munc13, membrane fusion, exocytosis |
| Biological source | Rattus norvegicus (Norway rat) More |
| Total number of polymer chains | 1 |
| Total formula weight | 130895.87 |
| Authors | Grushin, K.,Sindelar, C.V. (deposition date: 2021-12-15, release date: 2022-02-09, Last modification date: 2024-02-28) |
| Primary citation | Grushin, K.,Kalyana Sundaram, R.V.,Sindelar, C.V.,Rothman, J.E. Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release. Proc.Natl.Acad.Sci.USA, 119:-, 2022 Cited by PubMed Abstract: How can exactly six SNARE complexes be assembled under each synaptic vesicle? Here we report cryo-EM crystal structures of the core domain of Munc13, the key chaperone that initiates SNAREpin assembly. The functional core of Munc13, consisting of C1-C2B-MUN-C2C (Munc13C) spontaneously crystallizes between phosphatidylserine-rich bilayers in two distinct conformations, each in a radically different oligomeric state. In the open conformation (state 1), Munc13C forms upright trimers that link the two bilayers, separating them by ∼21 nm. In the closed conformation, six copies of Munc13C interact to form a lateral hexamer elevated ∼14 nm above the bilayer. Open and closed conformations differ only by a rigid body rotation around a flexible hinge, which when performed cooperatively assembles Munc13 into a lateral hexamer (state 2) in which the key SNARE assembly-activating site of Munc13 is autoinhibited by its neighbor. We propose that each Munc13 in the lateral hexamer ultimately assembles a single SNAREpin, explaining how only and exactly six SNARE complexes are templated. We suggest that state 1 and state 2 may represent two successive states in the synaptic vesicle supply chain leading to "primed" ready-release vesicles in which SNAREpins are clamped and ready to release (state 3). PubMed: 35135883DOI: 10.1073/pnas.2121259119 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (10 Å) |
Structure validation
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