SNARE Zippering Is Suppressed by a Conformational Constraint that Is Removed by v-SNARE Splitting.
SNARE Zippering Is Suppressed by a Conformational Constraint that Is Removed by v-SNARE Splitting.
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SNARE 拉链受到构象约束的抑制，而 v-SNARE 分裂消除了构象约束
DOI：
10.1016/j.celrep.2020.108611
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发表时间：
2021-01-12
期刊：
影响因子：
8.8
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Liu Y;Wan C;Rathore SS;Stowell MHB;Yu H;Shen J
胞内囊泡融合由可溶性N-乙基马来酰亚胺敏感因子附着蛋白受体（SNARE）催化。囊泡锚定的v-SNARE与靶膜相关的t-SNARE配对以形成反式SNARE复合物，释放自由能以驱动膜融合。然而，trans-SNARE复合物不能有效地组装，除非被Sec 1/Munc 18（SM）蛋白激活。在这里，我们证明了当v-SNARE分裂成两个片段时，SNARE变得完全活跃，消除了SM蛋白激活的需要。从机制上讲，v-SNARE分裂加速了trans-SNARE复合物的拉链，模拟了SM蛋白的刺激功能。因此，SNARE具有驱动有效膜融合的全部潜力，但受到构象约束的抑制。这种限制通过SM蛋白激活或v-SNARE分裂来消除。我们认为，祖先的SNARE最初进化到完全活跃的SM蛋白的情况下。后来，构象约束与SM蛋白共同进化，以实现复杂内膜系统所需的囊泡融合特异性。SNARE不能驱动有效的膜融合，除非被Sec 1/Munc 18（SM）蛋白激活。在这项工作中，Liu等人证明了v-SNARE分裂模拟SM蛋白活化并释放了SNARE的全部膜融合潜力。
Intracellular vesicle fusion is catalyzed by soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Vesicle-anchored v-SNAREs pair with target membrane-associated t-SNAREs to form trans-SNARE complexes, releasing free energy to drive membrane fusion. However, trans-SNARE complexes are unable to assemble efficiently unless activated by Sec1/Munc18 (SM) proteins. Here, we demonstrate that SNAREs become fully active when the v-SNARE is split into two fragments, eliminating the requirement of SM protein activation. Mechanistically, v-SNARE splitting accelerates the zippering of trans-SNARE complexes, mimicking the stimulatory function of SM proteins. Thus, SNAREs possess the full potential to drive efficient membrane fusion but are suppressed by a conformational constraint. This constraint is removed by SM protein activation or v-SNARE splitting. We suggest that ancestral SNAREs originally evolved to be fully active in the absence of SM proteins. Later, a conformational constraint coevolved with SM proteins to achieve the vesicle fusion specificity demanded by complex endomembrane systems. SNAREs are unable to drive efficient membrane fusion unless activated by Sec1/Munc18 (SM) proteins. In this work, Liu et al. demonstrate that v-SNARE splitting mimics SM protein activation and unleashes the full membrane fusion potential of SNAREs.
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影响因子：
16.6
作者：
Shen C;Rathore SS;Yu H;Gulbranson DR;Hua R;Zhang C;Schoppa NE;Shen J
通讯作者：
Shen J
影响因子：
16.2
作者：
Lai Y;Choi UB;Leitz J;Rhee HJ;Lee C;Altas B;Zhao M;Pfuetzner RA;Wang AL;Brose N;Rhee J;Brunger AT
通讯作者：
Brunger AT
DOI：
10.1126/science.1224492
发表时间：
2012-09-14
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gao Y;Zorman S;Gundersen G;Xi Z;Ma L;Sirinakis G;Rothman JE;Zhang Y
通讯作者：
Zhang Y
影响因子：
4
作者：
Dacks, Joel B.;Field, Mark C.
通讯作者：
Field, Mark C.
DOI：
10.1073/pnas.0611318104
发表时间：
2007-02-20
影响因子：
11.1
作者：
Dulubova, Irina;Khvotchev, Mikhail;Rizo, Josep
通讯作者：
Rizo, Josep