A role for the syntaxin N-terminus.
A role for the syntaxin N-terminus.
复制标题
DOI：
10.1042/bj20082389
复制
发表时间：
2009-02-15
期刊：
影响因子：
--
通讯作者：
Bryant, Nia J
中科院分区：
文献类型：
--
作者：
Munson, Mary;Bryant, Nia J
真核生物中的细胞内膜融合步骤需要SNARE（可溶性N-乙基马来酰亚胺敏感性融合蛋白-附着蛋白受体）蛋白的突触融合蛋白家族。突触融合蛋白通过与调节蛋白（包括SM（Sec 1 p/Munc 18）蛋白）相互作用在多个水平上受到调节。理解这种调节的关键是在分子水平上表征不同的SM-突触融合蛋白结合相互作用以及它们对体内功能的贡献。最保守的SM-突触融合蛋白结合模式是通过突触融合蛋白的末端N-末端肽与SM蛋白表面上的疏水口袋的相互作用。令人惊讶的是，两种不同的SM蛋白的突变体版本废除这种结合显示在体内没有可辨别的表型。在这一期的《生物化学杂志》上，约翰逊等人证明了突触融合蛋白<$64和SM蛋白<$18之间N-末端结合相互作用的丧失严重损害了秀丽隐杆线虫的神经肌肉突触传递，导致了不协调的表型。相比之下，SM-突触融合蛋白结合的第二模式的损失没有可检测的影响。总的来说，这些结果表明，虽然不同的膜运输步骤都受到SM-突触融合蛋白的相互作用，使用类似的结合模式，他们的差异调节，突出需要仔细解剖的结合模式。
Intracellular membrane fusion steps in eukaryotes require the syntaxin family of SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins. Syntaxins are regulated at several levels through interactions with regulatory proteins, including the SM (Sec1p/Munc18) proteins. Key to understanding this regulation is the characterization of different SM-syntaxin binding interactions at the molecular level and in terms of their contribution to function in vivo. The most conserved SM-syntaxin binding mode is through interaction of the syntaxin's extreme N-terminal peptide with a hydrophobic pocket on the surface of the SM protein. Surprisingly, mutant versions of two different SM proteins abrogated for this binding display no discernable phenotypes in vivo. In this issue of the Biochemical Journal, Johnson et al. demonstrate that loss of the N-terminal binding interaction between the syntaxin UNC-64 and the SM protein UNC-18 severely impairs neuromuscular synaptic transmission in Caenorhabditis elegans, resulting in an unco-ordinated phenotype. In contrast, loss of a second mode of SM-syntaxin binding has no detectable effect. Collectively, these results suggest that, although different membrane trafficking steps are all regulated by SM-syntaxin interactions using similar binding modes, they are differentially regulated, highlighting the need for careful dissection of the binding modes.