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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Syntaxin N-terminal peptide motif is an initiation factor for the assembly of the SNARE-Sec1/Munc18 membrane fusion complex
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Syntaxin N-terminal peptide motif is an initiation factor for the assembly of the SNARE-Sec1/Munc18 membrane fusion complex

机译:Syntaxin N末端肽基序是SNARE-Sec1 / Munc18膜融合复合物组装的起始因子

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摘要

Intracellular membrane fusion is mediated by the concerted action of W-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) and Sec1/Munc18 (SM) proteins. During fusion, SM proteins bind the N-terminal peptide (N-peptide) motif of the SNARE subunit syntaxin, but the function of this interaction is unknown. Here, using FRET-based biochemical reconstitution and Caenorhab-ditis elegans genetics, we show that the N-peptide of syntaxin-1 recruits the SM protein Munc18-1Sec1 to the SNARE bundle, facilitating their assembly into a fusion-competent complex. The recruitment is achieved through physical tethering rather than allosteric activation of Munci 8-1. Consistent with the recruitment role, the N-peptide is not spatially constrained along syntaxin-1, and it is functional when translocated to another SNARE subunit SNAP-25 or even when simply anchored in the target membrane. The N-peptide function is restricted to an early initiation stage of the fusion reaction. After association, Munc18-1 and the SNARE bundle together drive membrane merging without further involving the N-peptide. Thus, the syntaxin N-peptide is an initiation factor for the assembly of the SNARE-SM membrane fusion complex.
机译:W-乙基马来酰亚胺敏感因子附着蛋白受体(SNAREs)和Sec1 / Munc18(SM)蛋白的协同作用介导细胞内膜融合。在融合过程中,SM蛋白结合了SNARE亚基语法的N端肽(N肽)基序,但这种相互作用的功能尚不清楚。在这里,使用基于FRET的生化重组和秀丽隐杆线虫的遗传学,我们显示语法素1的N肽将SM蛋白Munc18-1 / nSec1募集到SNARE束中,从而促进它们组装成具有融合能力的复合物。招募是通过物理系留而非Munci 8-1的变构激活来实现的。与募集作用一致,N肽在空间上不受语法1约束,并且在易位到另一个SNARE亚基SNAP-25时,甚至在简单锚定在目标膜中时,它都具有功能。 N-肽功能限于融合反应的早期起始阶段。缔合后,Munc18-1和SNARE束一起驱动膜合并,而无需进一步牵涉N肽。因此,语法素N-肽是SNARE-SM膜融合复合物组装的起始因子。

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    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309;

    The Howard Hughes Medical Institute,Department of Biology, University of Utah, Salt Lake City, UT 84112;

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309;

    The Howard Hughes Medical Institute,Department of Biology, University of Utah, Salt Lake City, UT 84112;

    The Howard Hughes Medical Institute,Department of Biology, University of Utah, Salt Lake City, UT 84112;

    Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO 80309;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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