Lipid transfer proteins and instructive regulation of lipid kinase activities: Implications for inositol lipid signaling and disease.
Lipid transfer proteins and instructive regulation of lipid kinase activities: Implications for inositol lipid signaling and disease.
复制标题
DOI：
10.1016/j.jbior.2020.100740
复制
发表时间：
2020-12
影响因子：
--
通讯作者：
McDermott MI
中科院分区：
文献类型：
--
作者：
Lete MG;Tripathi A;Chandran V;Bankaitis VA;McDermott MI
细胞膜是细胞内信号传递的关键平台，涉及脂质和蛋白质之间的复杂界面，以及多种脂质代谢途径之间的相互作用网络。膜脂在调节回路中传递结构和功能信息，包括生物物理参数，如膜厚度和流动性，以及伴随蛋白质结合伙伴的相互作用。磷脂酰肌醇及其磷酸化衍生物，即磷酸肌醇，在细胞膜内信号传导中起着关键作用，这些作用被转化为一系列令人印象深刻的生物学结果。磷脂酰肌醇转移蛋白（PITPs）是磷脂肌醇信号传导的关键调控因子。从植物、酵母、顶复合体寄生虫到哺乳动物等多种生物中都有发现，pitp最初被认为是细胞膜间脂质的简单转运体。现在看来，这些蛋白质的可溶性版本在细胞内执行这种功能的可能性越来越小。相反，这些有助于促进内在生物学上不足的肌醇脂质激酶的活性，并以此促进磷酸肌苷信号传导的生物学结果的多样化。执行这些功能的核心引擎是脂质交换循环，这是pitp的基本特性。pitp如何进行脂质交换仍然知之甚少。分子动力学模拟方法现在提供了第一个关于pitp以及其他潜在的脂质交换/转移蛋白如何运作的原子性见解。
Cellular membranes are critical platforms for intracellular signaling that involve complex interfaces between lipids and proteins, and a web of interactions between a multitude of lipid metabolic pathways. Membrane lipids impart structural and functional information in this regulatory circuit that encompass biophysical parameters such as membrane thickness and fluidity, as well as chaperoning the interactions of protein binding partners. Phosphatidylinositol and its phosphorylated derivatives, the phosphoinositides, play key roles in intracellular membrane signaling, and these involvements are translated into an impressively diverse set of biological outcomes. The phosphatidylinositol transfer proteins (PITPs) are key regulators of phosphoinositide signaling. Found in a diverse array of organisms from plants, yeast and apicomplexan parasites to mammals, PITPs were initially proposed to be simple transporters of lipids between intracellular membranes. It now appears increasingly unlikely that the soluble versions of these proteins perform such functions within the cell. Rather, these serve to facilitate the activity of intrinsically biologically insufficient inositol lipid kinases and, in so doing, promote diversification of the biological outcomes of phosphoinositide signaling. The central engine for execution of such functions is the lipid exchange cycle that is a fundamental property of PITPs. How PITPs execute lipid exchange remains very poorly understood. Molecular dynamics simulation approaches are now providing the first atomistic insights into how PITPs, and potentially other lipid-exchange/transfer proteins, operate.
登录
查看更多内容
影响因子：
6.5
作者：
Alb, James G., Jr.;Phillips, Scott E.;Bankaitis, Vytas A.
通讯作者：
Bankaitis, Vytas A.
Drs2p的作用，P型ATPase和潜在的氨基磷脂易位酶，在高尔基酵母晚期功能中。
影响因子：
7.8
作者：
Chen, C Y;Ingram, M F;Rosal, P H;Graham, T R
通讯作者：
Graham, T R
影响因子：
4.8
作者：
Alb, JG;Cortese, JD;Bankaitis, VA
通讯作者：
Bankaitis, VA
影响因子：
4.8
作者：
Chang, Chi-Lun;Liou, Jen
通讯作者：
Liou, Jen
影响因子：
64.8
作者：
BANKAITIS, VA;AITKEN, JR;DOWHAN, W
通讯作者：
DOWHAN, W