气候变化领域集成服务门户(CCPortal): The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure

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DOI	10.1073/pnas.2014605118
	The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure
	Zhou Y.; Prakash P.S.; Liang H.; Gorfe A.A.; Hancock J.F.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	KRAS interacts with the inner leaflet of the plasma membrane (PM) using a hybrid anchor that comprises a lysine-rich polybasic domain (PBD) and a C-terminal farnesyl chain. Electrostatic interactions have been envisaged as the primary determinant of interactions between KRAS and membranes. Here, we integrated molecular dynamics (MD) simulations and superresolution spatial analysis in mammalian cells and systematically compared four equally charged KRAS anchors: the wild-type farnesyl hexa-lysine and engineered mutants comprising farnesyl hexa-arginine, geranylgeranyl hexa-lysine, and geranylgeranyl hexa-arginine. MD simulations show that these equally charged KRAS mutant anchors exhibit distinct interactions and packing patterns with different phosphatidylserine (PtdSer) species, indicating that prenylated PBD-bilayer interactions extend beyond electrostatics. Similar observations were apparent in intact cells, where each anchor exhibited binding specificities for PtdSer species with distinct acyl chain compositions. Acyl chain composition determined responsiveness of the spatial organization of different PtdSer species to diverse PM perturbations, including transmembrane potential, cholesterol depletion, and PM curvature. In consequence, the spatial organization and PM binding of each KRAS anchor precisely reflected the behavior of its preferred PtdSer ligand to these same PM perturbations. Taken together these results show that small GTPase PBD-prenyl anchors, such as that of KRAS, have the capacity to encode binding specificity for specific acyl chains as well as lipid headgroups, which allow differential responses to biophysical perturbations that may have biological and signaling consequences for the anchored GTPase. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Acyl chains; KRAS; Nanoclusters; Phosphatidylserine; Plasma membrane depolarization
语种	英语
scopus关键词	arginine; cholesterol; farnesyl hexa arginine; farnesyl hexa lysine; geranylgeranyl hexa arginine; geranylgeranyl hexa lysine; guanosine triphosphatase; K ras protein; lysine; phosphatidylserine; unclassified drug; Article; cell membrane; controlled study; electron microscopy; mammal cell; membrane potential; molecular dynamics; polybasic domain; prenylation; priority journal; protein domain; protein protein interaction; protein structure; spatial analysis; static electricity
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180693
作者单位	Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas, Health Science Center, Houston, TX 77030, United States; Graduate School of Biological Sciences, MD Anderson Cancer Center, University of Texas, Health Science Center, Houston, TX 77030, United States; NCI RAS Initiative, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD 21701, United States
推荐引用方式 GB/T 7714	Zhou Y.,Prakash P.S.,Liang H.,et al. The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure[J],2021,118(6).
APA	Zhou Y.,Prakash P.S.,Liang H.,Gorfe A.A.,&Hancock J.F..(2021).The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Zhou Y.,et al."The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).