Role of SNAREs in Membrane Fusion
Role of SNAREs in Membrane Fusion
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DOI：
10.1007/978-94-007-0763-4_3
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Jena, Bhanu P.
中科院分区：
文献类型：
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作者：
Jena, Bhanu P.
对立细胞膜之间的融合对于许多细胞活动如蛋白质成熟、神经传递、激素分泌和酶释放是必不可少的。膜融合的普遍分子机制涉及Ca2+，以及存在于对立膜双层中的一组特殊蛋白质的组装。例如，在细胞分泌中，细胞质膜上的靶膜蛋白SNAP-25和syntaxin称为t-SNAREs，以及分泌囊泡相关蛋白VAMP或v-SNARE都是参与对立膜融合的保守蛋白复合物的一部分。在Ca2+存在的情况下，t- snare和v-SNARE相互作用并自组装成环形构象，形成导电通道。这种t-/v-SNARE环的自组装只有在各自的snare与膜相结合时才会发生。圈套环复合体的大小取决于相对双层的曲率。SNARE环复合物的电子密度图和三维地形图表明，形成了一个环厚25埃、高42埃的防泄漏通道。确定了膜定向SNARE环复合物组装的机理和SNARE环尺寸的数学预测。x射线衍射测量和模拟研究进一步表明，膜相关的t- snare和v-SNARE克服了排斥力，使相反的膜接近在大约2.8埃的距离内。然后，钙能够桥接紧密相对的双层，导致水从水合Ca2+离子中释放出来，以及磷脂头基团上松散协调的水，导致膜不稳定和融合。
Fusion between opposing cellular membranes is essential for numerous cellular activities such as protein maturation, neurotransmission, hormone secretion, and enzyme release. The universal molecular mechanism of membrane fusion involves Ca2+, and the assembly of a specialized set of proteins present in the opposing membrane bilayers. For example in cell secretion, target membrane proteins at the cell plasma membrane SNAP-25 and syntaxin termed t-SNAREs, and secretory vesicle-associated protein VAMP or v-SNARE, are part of the conserved protein complex involved in fusion of opposing membranes. In the presence of Ca2+ , t-SNAREs and v-SNARE in opposing bilayers interact and self-assemble in a ring conformation, to form conducting channels. Such self-assembly of t-/v-SNARE ring occurs only when the respective SNAREs are in association with membrane. The size of the SNARE ring complex is dependent on the curvature of the opposing bilayers. Electron density map and 3-D topography of the SNARE ring complex, suggests the formation of a leak-proof channel measuring 25 angstrom in ring thickne, and 42 angstrom in heig. The mechanism of membrane-directed SNARE ring complex assembly, and the mathematical prediction of SNARE ring size, has been determined. X-ray diffraction measurements and simulation studies have further advanced that membrane-associated t-SNAREs and v-SNARE overcome repulsive forces to bring the opposing membranes close to within a distance of approximately 2.8 angstrom. Calcium is then able to bridge the closely apposed bilayers, leading to the release of water from hydrated Ca2+ ions as well as the loosely coordinated water at phospholipid head groups, leading to membrane destabilization and fusion.