Henry Wellcome Laboratory of Cell Biology, Division of Molecular and Cellular Biology, Davidson Building, Faculty of Biomedical and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
Biochem Soc Trans. 2010 Feb;38(Pt 1):209-12. doi: 10.1042/BST0380209.
Regulation and specificity of membrane trafficking are required to maintain organelle integrity while performing essential cellular transport. Membrane fusion events in all eukaryotic cells are facilitated by the formation of specific SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) complexes between proteins on opposing lipid bilayers. Although regulation of SNARE complex assembly is not well understood, it is clear that two conserved protein families, the Sx (syntaxin) and the SM (Sec1p/Munc18) proteins, are central to this process. Sxs are a subfamily of SNARE proteins; in addition to the coiled-coil SNARE motif, Sxs possess an N-terminal, autonomously folded, triple-helical (Habc) domain. For some Sxs, it has been demonstrated that this Habc domain exerts an autoinhibitory effect on SNARE complex assembly by making intramolecular contacts with the SNARE motif. SM proteins regulate membrane fusion through interactions with their cognate Sxs. One hypothesis for SM protein function is that they facilitate a switch of the Sx from a closed to an open conformation, thus lifting the inhibitory action of the Habc domain and freeing the SNARE motif to participate in SNARE complexes. However, whether these regulatory mechanisms are conserved throughout the Sx/SM protein families remains contentious as it is not clear whether the closed conformation represents a universal feature of Sxs.
膜运输的调节和特异性对于维持细胞器完整性和执行必要的细胞运输是必需的。所有真核细胞中的膜融合事件都是通过在 opposing lipid bilayers 上的蛋白质之间形成特定的 SNARE（可溶性 N-乙基马来酰亚胺敏感的融合蛋白附着蛋白受体）复合物来促进的。尽管 SNARE 复合物组装的调节机制尚不清楚，但很明显，两个保守的蛋白质家族，Sx（突触融合蛋白）和 SM（Sec1p/Munc18）蛋白，是这个过程的核心。Sxs 是 SNARE 蛋白的一个亚家族；除了卷曲螺旋 SNARE 基序外，Sxs 还具有一个 N 端、自主折叠的三螺旋（Habc）结构域。对于一些 Sxs，已经证明该 Habc 结构域通过与 SNARE 基序的分子内相互作用对 SNARE 复合物的组装施加自动抑制作用。SM 蛋白通过与它们的同源 Sxs 相互作用来调节膜融合。SM 蛋白功能的一个假设是它们促进 Sx 从封闭构象到开放构象的转变，从而消除 Habc 结构域的抑制作用，并使 SNARE 基序能够参与 SNARE 复合物。然而，这些调节机制是否在整个 Sx/SM 蛋白家族中都保守仍然存在争议，因为不清楚封闭构象是否代表 Sxs 的普遍特征。
