2M8R

Pre-Fusion Solution NMR Structure of Neuronal SNARE Syntaxin 1A

2M8R の概要

• エントリーDOI: 10.2210/pdb2m8r/pdb
• NMR情報: BMRB: 19266
• 分子名称: Syntaxin-1A (1 entity in total)
• 機能のキーワード: syntaxin, snare, prefusion, membrane protein
• 由来する生物種: Rattus norvegicus (brown rat,rat,rats)
• 細胞内の位置: Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Single-pass type IV membrane protein (By similarity): P32851
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 12334.40

構造登録者

Liang, B.,Kiessling, V.,Tamm, L.K. (登録日: 2013-05-24, 公開日: 2013-11-20, 最終更新日: 2024-05-01)

主引用文献

Liang, B.,Kiessling, V.,Tamm, L.K.
Prefusion structure of syntaxin-1A suggests pathway for folding into neuronal trans-SNARE complex fusion intermediate.
Proc.Natl.Acad.Sci.USA, 110:19384-19389, 2013

PubMed Abstract: The assembly of the three neuronal soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins synaptobrevin 2, syntaxin-1A, and SNAP-25 is the key step that leads to exocytotic fusion of synaptic vesicles. In the fully assembled SNARE complex, these three proteins form a coiled-coil four-helix bundle structure by interaction of their respective SNARE motifs. Although biochemical and mutational analyses strongly suggest that the heptad-repeat SNARE motifs zipper into the final structure, little is known about the prefusion state of individual membrane-bound SNAREs and how they change conformation from the unzippered prefusion to the zippered postfusion state in a membrane environment. We have solved the solution NMR structure of micelle-bound syntaxin-1A in its prefusion conformation. In addition to the transmembrane helix, the SNARE motif consists of two well-ordered, membrane-bound helices separated by the "0-layer" residue Gln226. This unexpected structural order of the N- and C-terminal halves of the uncomplexed SNARE motif suggests the formation of partially zippered SNARE complex intermediates, with the 0-layer serving as a proofreading site for correct SNARE assembly. Interferometric fluorescence measurements in lipid bilayers confirm that the open SNARE motif helices of syntaxin interact with lipid bilayers and that association with the other target-membrane SNARE SNAP-25 lifts the SNARE motif off the membrane as a critical prerequisite for SNARE complex assembly and membrane fusion.

PubMed: 24218570
DOI: 10.1073/pnas.1314699110

実験手法

SOLUTION NMR