Lipid chain-driven interaction of a lipidated Src-family kinase Lyn with the bilayer membrane
Lipid chain-driven interaction of a lipidated Src-family kinase Lyn with the bilayer membrane
复制标题
脂化 Src 家族激酶 Lyn 与双层膜的脂链驱动相互作用
DOI：
10.1039/d2ob01079h
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发表时间：
2022
影响因子：
3.2
通讯作者：
Hojo Hironobu
中科院分区：
文献类型：
--
作者：
Hanashima Shinya;Mito Kanako;Umegawa Yuichi;Murata Michio;Hojo Hironobu
N-肉豆蔻酰化是一种普遍存在的蛋白质修饰过程，它与可逆的S棕榈酰化反应一起促进细胞表面脂化蛋白的相互作用。我们报道了两个酰基蛋白质链的协同脂-脂相互作用，这增加了蛋白质-膜的相互作用，并促进了含有阴离子脂类的膜的选择性靶向。Lyn是Src家族的一员，通过N-肉豆蔻酰基和邻近的S-棕榈酰基链锚定在膜表面唯一的N-末端结构域上分布。我们制备了脂化Lyn的N端短片段，通过固体核磁共振分析研究了每个酰基链在脂类组成相关的膜相互作用中的行为。固体31P-核磁共振研究表明，N-肉豆蔻酰化LYN多肽的S棕榈酰化增强了多肽与磷脂头部基团之间的相互作用，特别是与含有磷脂酰丝氨酸的阴离子双层之间的相互作用。固体~2H-核磁共振谱表明，在邻位的S棕榈酸链的存在下，N-肉豆蔻基链的长度增加(0.6~0.8)，可能是通过酰基链的相互作用。Lyn的两个酰基链的协同碳链相互作用通过将碳链延伸到膜内部更深的位置来增加膜的结合力，从而促进了阳离子多肽侧链和阴离子脂头基团之间的肽-膜表面相互作用。S棕榈酰化的这种脂质驱动机制促进了脂化蛋白向细胞膜表面的分配，并可能参与了在富含阴离子脂类的信号域招募Lyn的过程。
N-Myristoylation is a process of ubiquitous protein modification, which promotes the interaction of lipidated proteins on cell surfaces, in conjunction with reversible S-palmitoylation. We report the cooperative lipid–lipid interaction of two acyl chains of proteins, which increases the protein–membrane interaction and facilitates selective targeting of membranes containing anionic lipids. Lyn is a member of the Src family kinases distributed on the membrane surface by N-myristoyl and neighbouring S-palmitoyl chain anchors at the unique N-terminus domain. We prepared N-terminal short segments of lipidated Lyn to investigate the behaviour of each acyl chain in the lipid composition-dependent membrane interaction by solid-state nuclear magnetic resonance (NMR) analysis. Solid-state 31P-NMR studies revealed that S-palmitoylation of N-myristoylated Lyn peptides increased the interaction between peptides and phospholipid head groups, particularly with the anionic phosphatidylserine-containing bilayers. The solid-state 2H-NMR of Lyn peptides with a perdeutero N-myristoyl chain indicated an increase (0.6–0.8 Å) in the extent of the N-myristoyl chain in the presence of nearby S-palmitoyl chains, probably through the interaction via the acyl chains. The cooperative hydrocarbon chain interaction of the two acyl chains of Lyn increased membrane binding by extending the hydrocarbon chains deeper into the membrane interior, thereby promoting the peptide–membrane surface interaction between the cationic peptide side chains and the anionic lipid head groups. This lipid-driven mechanism by S-palmitoylation promotes the partition of the lipidated proteins to the cytoplasmic surface of the cell membranes and may be involved in recruiting Lyn at the signalling domains rich in anionic lipids.