7T7X

Munc13-1 C1-C2B-MUN-C2C Upright conformation spanning two lipid bilayers

7T7X の概要

• エントリーDOI: 10.2210/pdb7t7x/pdb
• 関連するPDBエントリー: 7T7C 7T7R
• EMDBエントリー: 25738 25740
• 分子名称: Protein unc-13 homolog A (1 entity in total)
• 機能のキーワード: synaptic transmission, munc13, membrane fusion, exocytosis
• 由来する生物種: Rattus norvegicus (Norway rat); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 130895.87

構造登録者

Grushin, K.,Sindelar, C.V. (登録日: 2021-12-15, 公開日: 2022-02-09, 最終更新日: 2024-02-28)

主引用文献

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

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: 35135883
DOI: 10.1073/pnas.2121259119

実験手法

ELECTRON MICROSCOPY (10 Å)