Penetratin-membrane association: W48/R52/W56 shield the peptide from the aqueous phase
Penetratin-membrane association: W48/R52/W56 shield the peptide from the aqueous phase
复制标题
DOI：
10.1529/biophysj.104.052787
复制
发表时间：
2005-02-01
影响因子：
3.4
通讯作者：
Rosseneu, M
中科院分区：
文献类型：
--
作者：
Lensink, MF;Christiaens, B;Rosseneu, M
利用分子动力学模拟，我们研究了细胞穿透肽穿透素与中性和带电双分子层的关联模式。结果表明，肽脂初始结合是一个由静电相互作用驱动的快速过程。带正电的残基沿螺旋肽轴均匀分布，特别是残基K46、R53和K57，有助于肽与脂质的关联。双分子层增强了穿透蛋白螺旋的稳定性。平行于脂水界面，肽通过双分子层头基团的插入速度明显减慢。带负电荷的脂质大大增强了肽的结合。横向侧链运动为螺旋进入膜的疏水核心创造了一个开口。肽芳香族残基通过W48/R52/W56和F49/R53形成pi堆叠簇，保护肽不受水相的影响。与穿透素肽的相互作用对整个膜结构的影响有限，因为它主要影响直接与肽相互作用的脂质的构象。局部电荷匹配增加带负电荷的脂质浓度，局部脂质横向扩散减少。脂质紊乱增加，通过降低有序参数的脂质与渗透蛋白侧链相互作用。膜表面的穿透素分子似乎不聚集。
Using molecular dynamics simulations, we studied the mode of association of the cell-penetrating peptide penetratin with both a neutral and a charged bilayer. The results show that the initial peptide-lipid association is a fast process driven by electrostatic interactions. The homogeneous distribution of positively charged residues along the axis of the helical peptide, and especially residues K46, R53, and K57, contribute to the association of the peptide with lipids. The bilayer enhances the stability of the penetratin helix. Oriented parallel to the lipid-water interface, the subsequent insertion of the peptide through the bilayer headgroups is significantly slower. The presence of negatively charged lipids considerably enhances peptide binding. Lateral side-chain motion creates an opening for the helix into the hydrophobic core of the membrane. The peptide aromatic residues form a pi-stacking cluster through W48/R52/W56 and F49/R53, protecting the peptide from the water phase. Interaction with the penetratin peptide has only limited effect on the overall membrane structure, as it affects mainly the conformation of the lipids which interact directly with the peptide. Charge matching locally increases the concentration of negatively charged lipids, lateral lipid diffusion locally decreases. Lipid disorder increases, through decreased order parameters of the lipids interacting with the penetratin side chains. Penetratin molecules at the membrane surface do not seem to aggregate.