Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Adv Exp Med Biol. 2011;713:13-32. doi: 10.1007/978-94-007-0763-4_3.
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 Ca(2+), 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 Ca(2+), 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 Å in ring thickness, and 42 Å in height. 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 Å. Calcium is then able to bridge the closely apposed bilayers, leading to the release of water from hydrated Ca(2+) ions as well as the loosely coordinated water at phospholipid head groups, leading to membrane destabilization and fusion.
细胞的细胞膜融合对于许多细胞活动是必不可少的，如蛋白质成熟、神经递质传递、激素分泌和酶释放。膜融合的普遍分子机制涉及 Ca(2+)，以及存在于 opposing membrane bilayers 中的一组特殊蛋白质的组装。例如，在细胞分泌中，质膜 SNAP-25 和突触小体相关蛋白 syntaxin 称为 t-SNAREs，以及分泌小泡相关蛋白 VAMP 或 v-SNARE，是参与 opposing membranes 融合的保守蛋白质复合物的一部分。在 Ca(2+)存在下，opposing bilayers 中的 t-SNAREs 和 v-SNARE 相互作用并自组装成环状构象，形成导电通道。只有当相应的 SNAREs 与膜结合时，才会发生这种 t-/v-SNARE 环的自组装。SNARE 环复合物的大小取决于 opposing bilayers 的曲率。SNARE 环复合物的电子密度图和 3-D 拓扑结构表明，形成了一个无泄漏通道，其环厚度为 25Å，高度为 42Å。已经确定了膜定向 SNARE 环复合物组装的机制，以及 SNARE 环大小的数学预测。X 射线衍射测量和模拟研究进一步表明，membrane-associated t-SNAREs 和 v-SNARE 克服排斥力，使 opposing membranes 接近到大约 2.8Å 的距离。然后，Ca(2+)能够桥接紧密相邻的双层膜，导致从水合 Ca(2+)离子以及磷脂头部基团中松散配位的水中释放出水，导致膜不稳定和融合。
