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Chaperoning SNARE Folding and Assembly
Annual Review of Biochemistry ( IF 12.1 ) Pub Date : 2021-06-21 , DOI: 10.1146/annurev-biochem-081820-103615
Yongli Zhang 1 , Frederick M Hughson 2
Affiliation  

SNARE proteins and Sec1/Munc18 (SM) proteins constitute the core molecular engine that drives nearly all intracellular membrane fusion and exocytosis. While SNAREs are known to couple their folding and assembly to membrane fusion, the physiological pathways of SNARE assembly and the mechanistic roles of SM proteins have long been enigmatic. Here, we review recent advances in understanding the SNARE–SM fusion machinery with an emphasis on biochemical and biophysical studies of proteins that mediate synaptic vesicle fusion. We begin by discussing the energetics, pathways, and kinetics of SNARE folding and assembly in vitro. Then, we describe diverse interactions between SM and SNARE proteins and their potential impact on SNARE assembly in vivo. Recent work provides strong support for the idea that SM proteins function as chaperones, their essential role being to enable fast, accurate SNARE assembly. Finally, we review the evidence that SM proteins collaborate with other SNARE chaperones, especially Munc13-1, and briefly discuss some roles of SNARE and SM protein deficiencies in human disease.

中文翻译:



陪伴 SNARE 折叠和组装



SNARE蛋白和Sec1/Munc18 (SM)蛋白构成驱动几乎所有细胞内膜融合和胞吐作用的核心分子引擎。虽然已知 SNARE 将其折叠和组装与膜融合耦合,但 SNARE 组装的生理途径和 SM 蛋白的机制作用长期以来一直是个谜。在这里,我们回顾了理解 SNARE-SM 融合机制的最新进展,重点是介导突触小泡融合的蛋白质的生化和生物物理研究。我们首先讨论 SNARE 体外折叠和组装的能量学、途径和动力学。然后,我们描述了 SM 和 SNARE 蛋白之间的多种相互作用及其对体内 SNARE 组装的潜在影响。最近的工作为 SM 蛋白作为伴侣的观点提供了强有力的支持,它们的重要作用是实现快速、准确的 SNARE 组装。最后,我们回顾了 SM 蛋白与其他 SNARE 伴侣,尤其是 Munc13-1 协同作用的证据,并简要讨论了 SNARE 和 SM 蛋白缺陷在人类疾病中的一些作用。

更新日期:2021-06-22
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