Human opioid peptide Met-enkephalin binds to anionic phosphatidylserine in high preference to zwitterionic phosphatidylcholine:: Natural-abundance 13C NMR study on the binding state in large unilamellar vesicles
Human opioid peptide Met-enkephalin binds to anionic phosphatidylserine in high preference to zwitterionic phosphatidylcholine:: Natural-abundance 13C NMR study on the binding state in large unilamellar vesicles
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DOI：
10.1021/bi061641v
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发表时间：
2006-12-26
期刊：
影响因子：
2.9
通讯作者：
Kimura, Tomohiro
中科院分区：
文献类型：
--
作者：
Kimura, Tomohiro
没有净电荷的人阿片样神经肽Met-脑啡肽（M-Enk：Tyr（1）-Gly（2）-Gly（3）-Phe（4）-Met（5））与阴离子磷脂酰丝氨酸（PS）的结合优先于两性离子磷脂酰胆碱（PC）。在PS和PC双层的结合机制进行了研究的基础上获得的自然丰度的C-13核磁共振（NMR）的肽的分子间和分子内相互作用的数据。C-13共振显着的高场变化，观察到在C-末端残基结合PS后，而没有这样的显着变化，观察到结合PC。高场化学位移的变化与其特征碳网站的依赖性归因于肽C-末端CO2-和PS头基NH3+之间的静电结合。尽管PS双层表面的净负电荷，M-Enk因此锚定带负电荷的C-末端。在N-末端残基，另一方面，显着的低场化学位移的变化后，观察到结合到PS和PC双层，PS系统中的变化幅度要大得多。低场变化与其特征性碳位点依赖性归因于肽N-末端NH 3+与脂质头基负电荷（PS中的CO2-或PO 4-，PC中的PO 4-）之间的静电结合。由于膜结合而对信号半宽的扰动也表明M-Enk在PS膜表面上比在PC膜表面上优先且更深地结合。局部电荷抵消有效地发生在M-Enk末端和PS头基之间，并补偿离子基团的强静电水合作用。头基中带电（正和负）和不带电位点沿沿着双层法线的分布是PS和PC头基在控制两性离子M-Enk的结合状态方面的显著差异的原因。
A human opioid neuropeptide, Met-enkephalin (M-Enk: Tyr(1)-Gly(2)-Gly(3)-Phe(4)-Met(5)), having no net charge binds to anionic phosphatidylserine (PS) in high preference to zwitterionic phosphatidylcholine (PC). The binding mechanism in the PS and PC bilayers was studied on the basis of the inter- and intramolecular interaction data obtained by natural-abundance C-13 nuclear magnetic resonance (NMR) of the peptide. Prominent upfield changes of the C-13 resonance were observed in the C-terminal residue upon binding to PS, whereas no such marked change was observed upon binding to PC. The upfield chemical shift changes with their characteristic carbon site dependence are ascribed to the electrostatic binding between the peptide C-terminal CO2- and the PS headgroup NH3+. Despite the net negative charge of the PS bilayer surface, M-Enk thus anchors the negatively charged C-terminus. In the N-terminal residue, on the other hand, marked downfield chemical shift changes are observed upon binding to both the PS and PC bilayers, the magnitude of the changes being much larger in the PS system. The downfield changes with their characteristic carbon site dependence are ascribed to the electrostatic binding between the peptide N-terminal NH3+ and the lipid headgroup negative charge(s) (CO2- or PO4- in PS, PO4- in PC). Perturbation on the signal half-widths due to membrane binding also indicates the preferential and deeper binding of M-Enk on the PS membrane surface than on the PC membrane surface. Local charge cancellation takes place efficiently between M-Enk termini and the PS headgroups and compensates for the strong electrostatic hydration of the ionic groups. Distribution of the charged (positive and negative) and uncharged sites in the headgroups along the bilayer normal is responsible for the marked difference between PS and PC headgroups in controlling the binding state of the zwitterionic M-Enk.