Lipid Binding to the Tail Domain of Vinculin
Lipid Binding to the Tail Domain of Vinculin
复制标题
脂质与纽蛋白尾部结构域的结合
DOI：
--
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发表时间：
2009
影响因子：
4.8
通讯作者：
S. Campbell
中科院分区：
文献类型：
--
作者：
S. M. Palmer;M. Playford;S. Craig;M. Schaller;S. Campbell
肌动蛋白是一种高度保守和丰富的细胞骨架蛋白，参与在细胞粘附位点将肌动蛋白细胞骨架连接到细胞膜。在这些粘附位点，黏着斑蛋白在生理过程中起作用，如细胞运动、迁移、发育和伤口愈合。正常黏着斑蛋白功能的丧失与癌症表型、心血管疾病和胚胎发生中的致命错误有关。黏着斑蛋白的尾部结构域（Vt）与酸性磷脂结合，并被认为在黏着斑蛋白活化和粘着斑转换中发挥作用。为了更好地表征Vt-脂质特异性，我们进行了一系列脂质共沉降实验，发现在混合脂质囊泡的背景下，与磷脂酰乙醇胺（PE）、磷脂酰胆碱（PC）、磷脂酰丝氨酸（PS）或磷脂酰肌醇（PI）相比，Vt显示与磷脂酰肌醇4，5-二磷酸（PIP 2）的特异性关联。已经提出Vt的C末端对于PIP 2缔合是重要的，因为C末端内的各种突变和缺失减少PIP 2缔合。脂质共沉降和NMR分析表明，疏水发夹的去除不改变Vt结构或PIP 2缔合。然而，C-末端内更广泛的缺失引入Vt结构扰动并降低PIP 2结合。有趣的是，对于干扰N-末端条带和螺旋束之间的相互作用的多种Vt变体，观察到PIP 2结合的显著增加，这表明该N-末端条带的重排可能是PIP 2结合所需的。
Vinculin is a highly conserved and abundant cytoskeletal protein involved in linking the actin cytoskeleton to the cell membrane at sites of cellular adhesion. At these sites of adhesion, vinculin plays a role in physiological processes such as cell motility, migration, development, and wound healing. Loss of normal vinculin function has been associated with cancer phenotypes, cardiovascular disease, and lethal errors in embryogenesis. The tail domain of vinculin (Vt) binds to acidic phospholipids and has been proposed to play a role in vinculin activation and focal adhesion turnover. To better characterize Vt-lipid specificity, we conducted a series of lipid co-sedimentation experiments and find that Vt shows specific association with phosphatidylinositol 4,5-bisphosphate (PIP2), compared with phosphatidylethanolamine (PE), phosphatidylcholine (PC), phosphatidylserine (PS), or phosphatidylinositol (PI) in the context of mixed lipid vesicles. The C terminus of Vt has been proposed to be important for PIP2 association, as various mutations and deletions within the C-terminal reduce PIP2 association. Lipid co-sedimentation and NMR analyses indicate that removal of the hydrophobic hairpin does not alter Vt structure or PIP2 association. However, more extensive deletions within the C-terminal introduce Vt structural perturbations and reduce PIP2 binding. Intriguingly, a significant increase in PIP2 binding was observed for multiple Vt variants that perturb interactions between the N-terminal strap and helix bundle, suggesting that a rearrangement of this N-terminal strap may be required for PIP2 binding.
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影响因子：
4
作者：
Lorca RA;Prabagaran M;England SK
通讯作者：
England SK
影响因子：
7.5
作者：
Delon, Isabelle;Brown, Nicholas H.
通讯作者：
Brown, Nicholas H.
纽蛋白头部和尾部结构域之间的分子内关联调节踝蛋白结合。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Johnson,RP;Craig,SW
通讯作者：
Craig,SW
影响因子：
4.6
作者：
Weiming Xu;H. Baribault;E. Adamson
通讯作者：
Weiming Xu;H. Baribault;E. Adamson
DOI：
10.1073/pnas.92.20.9161
发表时间：
1995-09-26
影响因子：
11.1
作者：
COLL, JL;BENZEEV, A;ADAMSON, ED
通讯作者：
ADAMSON, ED