PHOSPHOLIPID BINDING BY A SYNAPTIC VESICLE PROTEIN HOMOLOGOUS TO THE REGULATORY REGION OF PROTEIN KINASE-C
PHOSPHOLIPID BINDING BY A SYNAPTIC VESICLE PROTEIN HOMOLOGOUS TO THE REGULATORY REGION OF PROTEIN KINASE-C
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DOI：
10.1038/345260a0
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发表时间：
1990-05-17
期刊：
影响因子：
64.8
通讯作者：
SUDHOF, TC
中科院分区：
文献类型：
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作者：
PERIN, MS;FRIED, VA;SUDHOF, TC
神经递质在突触中通过Ca2+调节的突触囊泡胞吐释放，突触囊泡是储存高浓度神经递质的专门分泌细胞器1,2。快速Ca2+触发的突触囊泡融合可能是由特定的蛋白质介导的，这些蛋白质必须与Ca2+和磷脂双分子层相互作用。我们现在报道p65的细胞质结构域（一种结合钙调蛋白4的突触囊泡特异性蛋白3）包含一个内部重复序列，该序列与蛋白激酶C (PKC)5的调节c2区域同源。重组p65的细胞质结构域与酸性磷脂结合，具有特异性，表明p65与疏水核心以及磷脂的头基团相互作用。结合特异性类似于PKC，除了p65也结合钙调蛋白，将c2区域置于与PKC不同的潜在Ca2+调节的背景下。这是细胞蛋白与蛋白激酶c调控域之间的一种新的同源性。p65的结构和性质表明它可能在突触囊泡胞吐过程中介导膜相互作用。
NEUROTRANSMITTERS are released at synapses by the Ca2+-regulated exocytosis of synaptic vesicles, which are specialized secretory organelles that store high concentrations of neurotransmitters1,2. The rapid Ca2+-triggered fusion of synaptic vesicles is presumably mediated by specific proteins that must interact with Ca2+and the phospholipid bilayer. We now report that the cytoplasmic domain of p65, a synaptic vesicle-specific protein3that binds calmodulin4contains an internally repeated sequence that is homologous to the regulatory C2-region of protein kinase C (PKC)5. The cytoplasmic domain of recombinant p65 binds acidic phospholipids with a specificity indicating an interaction of p65 with the hydrophobic core as well as the headgroups of the phospholipids. The binding specificity resembles PKC, except that p65 also binds calmodulin, placing the C2-regions in a context of potential Ca2+-regulation that is different from PKC. This is a novel homology between a cellular protein and the regulatory domain of protein kinase C. The structure and properties of p65 suggest that it may have a role in mediating membrane interactions during synaptic vesicle exocytosis.