Vam3p structure reveals conserved and divergent properties of syntaxins
Vam3p structure reveals conserved and divergent properties of syntaxins
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DOI：
10.1038/85012
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发表时间：
2001-03-01
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影响因子：
--
通讯作者：
Rizo, J
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文献类型：
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作者：
Dulubova, I;Yamaguchi, T;Rizo, J
Synaxins和Sec1/Munc18蛋白是细胞膜融合的中心。所有的合成素都包括一个可变的N-末端区域，一个保守的对SNAR复合体形成至关重要的SNAR基序，以及一个跨膜区。神经元合成素1A的N-末端区域包含一个三螺旋结构域，该结构域折叠回到SNARE基序上形成一种‘闭合’构象；这种构象是Munc18-1结合所必需的。我们通过对空泡融合所必需的酵母合成素Vam3p的核磁共振分析，检验了合成素结构性质的共性，令人惊讶的是，Vam3p也具有一个N端的三螺旋结构域，尽管该区域与Synaxin 1A缺乏明显的序列同源性。然而，Vam3p不形成封闭的构象，其N-末端结构域不需要与Sec1/Munc18蛋白Vps33p结合，这表明Synaxins调控不同类型膜融合的机制存在关键差异。
Syntaxins and Sec1/munc18 proteins are central to intracellular membrane fusion. All syntaxins comprise a variable N-terminal region, a conserved SNARE motif that is critical for SNARE complex formation, and a transmembrane region. The N-terminal region of neuronal syntaxin 1A contains a three-helix domain that folds back onto the SNARE motif forming a 'closed' conformation; this conformation is required for munc18-1 binding. We have examined the generality of the structural properties of syntaxins by NMR analysis of Vam3p, a yeast syntaxin essential for vacuolar fusion, Surprisingly, Vam3p also has an N-terminal three-helical domain despite lacking apparent sequence homology with syntaxin 1A in this region. However, Vam3p does not form a closed conformation and its N-terminal domain is not required for binding to the Sec1/munc18 protein Vps33p, suggesting that critical distinctions exist in the mechanisms used by syntaxins to govern different types of membrane fusion.