Secretory and viral fusion may share mechanistic events with fusion between curved lipid bilayers
Secretory and viral fusion may share mechanistic events with fusion between curved lipid bilayers
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DOI：
10.1073/pnas.95.16.9274
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发表时间：
1998-08-04
影响因子：
11.1
通讯作者：
Lentz, BR
中科院分区：
文献类型：
--
作者：
Lee, J;Lentz, BR
据报道，分泌和病毒融合的各个步骤的活化能很大[Oberhauser，A. J，J，R. &费尔南德斯，J，M，（1992）生物物理学。J. 61，800-809; Clague，M，J，，Schoch，C，，Zech，L，&布卢门塔尔，R.（1990）Biochemistry 29，1303-1308]。了解这些大的活化能的原因是至关重要的，以确定这两种类型的生物膜融合的机制，我们最近表明，无蛋白质模型脂质双层的融合模仿分泌和病毒融合过程中观察到的步骤的顺序，这表明这些过程mag涉及常见的脂质，而不是蛋白质，重排。为了测试这种可能性，我们确定了三个步骤的活化能，我们能够区分这三个步骤有助于无蛋白模型脂质双层的融合。与可逆的第一中间体的形成相关的脂质重排的活化能，与其转化为半稳定的第二中间体相关的活化能，以及与不可逆的融合孔形成相关的活化能分别为37 kcal/mol，27 kcal/mol，和22 kcal/mol。第一个和最后一个这些是比较的活化能观察到的膜脂质交换（42千卡/摩尔）在病毒融合和分泌颗粒释放（23千卡/摩尔）的融合孔开放的速率，这种惊人的相似性强烈表明，参与分泌和病毒融合的基本分子过程涉及一组脂质分子重排，也参与模型膜融合。
Activation energies for the individual steps of secretory and viral fusion are reported to he large [Oberhauser, A. F,, Monck, J, R. & Fernandez, J, M, (1992) Biophys. J. 61, 800-809; Clague, M, J,, Schoch, C,, Zech, L, & Blumenthal, R. (1990) Biochemistry 29, 1303-1308]. Understanding the cause for these large activation energies is crucial to defining the mechanisms of these two types of biological membrane fusion, We showed recently that the fusion of protein-free model lipid bilayers mimics the sequence of steps observed during secretory and viral fusion, suggesting that these processes mag involve common lipid, rather than protein, rearrangements. To test for this possibility, we determined the activation energies for the three steps that we were able to distinguish as contributing to the fusion of protein-free model lipid bilayers, Activation energies for lipid rearrangements associated with formation of the reversible first intermediate, with conversion of this to a semi-stable second intermediate, and with irreversible fusion pore formation were 37 kcal/mol, 27 kcal/moI, and 22 kcal/mol, respectively. The first and last of these were comparable to the activation energies observed for membrane lipid exchange (42 kcal/moI) during viral fusion and for the rate of fusion pore opening during secretory granule release (23 kcal/mol), This striking similarity suggests strongly that the basic molecular processes involved in secretory and viral fusion involve a set of lipid molecule rearrangements that also are involved in model membrane fusion.