Membrane domain formation by calcium-dependent, lipid-binding proteins: insights from the C2 motif.
Membrane domain formation by calcium-dependent, lipid-binding proteins: insights from the C2 motif.
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钙依赖性脂质结合蛋白形成膜结构域：来自 C2 基序的见解。
DOI：
10.1016/s0167-4889(98)00146-3
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Creutz,CE
中科院分区：
文献类型：
--
作者：
Hinderliter,AK;Almeida,PF;Biltonen,RL;Creutz,CE
我们提出了一些膜结合蛋白，特别是C2基序在细胞功能中的新作用。C2基序以受Ca 2+调节的方式结合磷脂，并被认为赋予多种蛋白质膜结合能力，主要是参与信号转导和膜运输事件的蛋白质。我们假设，在Ca 2+的情况下，C2基序耦合的自由能结合到由两性离子和带负电荷的脂质组成的双层膜的形成富含负脂质的结构域。这又导致结合的同源或异源蛋白质的动态聚类，这些蛋白质包含C2基序或其他酸性脂质结合基序。在Ca 2+存在下，蛋白质簇可以进一步稳定。为了支持这一假设，我们提出的证据，膜结构域形成的第一个C2结构域的突触结合蛋白在没有Ca 2+。流体状态的磷脂混合物，结合芘标记的磷脂探针表现出芘准分子/单体荧光比的变化与域的形成后，结合C2域。此外，我们提出的C2结构域与膜的相互作用的模拟结果表明，蛋白质簇和脂质结构域形成一致。
We propose a novel role in cellular function for some membrane-binding proteins and, specifically, the C2 motif. The C2 motif binds phospholipid in a manner that is modulated by Ca2+and is thought to confer membrane-binding ability on a wide variety of proteins, primarily proteins involved in signal transduction and membrane trafficking events. We hypothesize that in the absence of Ca2+the C2 motif couples the free energy of binding to a bilayer membrane comprised of zwitterionic and negatively charged lipids to the formation of a domain enriched in the negative lipids. This in turn leads to the dynamic clustering of bound homologous or heterologous proteins incorporating the C2 motif, or other acidic lipid-binding motifs. In the presence of Ca2+, the protein clusters may be further stabilized. In support of this hypothesis we present evidence for membrane domain formation by the first C2 domain of synaptotagmin in the absence of Ca2+. Fluid state phospholipid mixtures incorporating a pyrene-labeled phospholipid probe exhibited a change in pyrene excimer/monomer fluorescence ratio consistent with domain formation upon binding the C2 domain. In addition, we present the results of simulations of the interaction of the C2 domain with the membrane that indicate that protein clusters and lipid domains form in concert.