髓鞘碱性蛋白对不同头部基团的髓磷脂质单层膜影响的热力学特性

Different Head Group Dependence on the Lipid Thermodynamic Property of the Myelin Basic Protein in the Lipid Monolayer

髓鞘碱性蛋白(myelin basic protein, MBP)是中枢神经系统(central nervous system, CNS)髓鞘成熟期的主要蛋白质之一。研究资料表明,MBP与变态反应性脑脊髓炎(allergic encephalomyelitis, EAE)、多发性硬化等多种神经疾病有关,是反映中枢神经系统有无实质性损害,有无髓鞘脱失的1个特异生化指标。18.5 kD的MBP与髓鞘膜的磷脂分子间的相互作用可以维持髓鞘结构的紧密性和稳定性。本文利用Langmuir-Blodgett (LB)技术研究了特定浓度下,MBP对髓鞘主要脂质(1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱(POPC)、1-棕榈酰-2-油酰-sn-甘油-3-磷酸乙醇胺(POPE)和1-棕榈酰-2-油酰-sn-甘油-3-磷酸丝氨酸(POPS))单层膜影响的热力学理论研究。热力学理论预测,在低的表面压力下,MBP与髓磷脂头部基团间发生相互作用,并阐述了第二维里系数和不同头部基团的髓磷脂之间的依赖关系。二维里数状态方程结果表明,MBP与髓磷脂相互作用的单层膜结构中的相互作用为排斥力,诱导单层膜发生相变,这与原子力显微镜(AFM)对MBP诱导的髓磷脂质单层膜表面构象变化的观测一致。所以,研究仿生膜有利于分析生物膜各个组分独立的功能,从而进一步揭示天然生物膜的奥秘有重要的指导意义。本课题对髓鞘碱性蛋白与髓磷脂膜分子间的相互作用机制的研究对神经中枢疾病的预估具有重要的生物学意义和医学价值。

The 18.5 kD myelin basic protein(MBP)isoform interacts with phospholipids and its role has been thought to maintain the stability and compactness of the myelin sheath structure.In this study,we describe the statistical thermodynamic theory of certain concentration effects on MBP in the major myelin lipid(1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine(POPC),1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethano-lamine(POPE),and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine(POPS))monolayers at the air/subphase interface via the Langmuir-Blodgett(LB)technique.A simple statistical mechanical theory is established that predicts the interaction between proteins and phosphate head groups at low surface pressures and the second virial coefficient dependences for the PC,PE,and PS head groups are illustrated.Two-dimensional virial equation of state(2D-VES)suggested that the interaction in the monolayer structure at the MBP-myelin interface is a repulsive force,and it induces a phase change in the monolayer.This is consistent with atomic force microscope(AFM)observations of domain and aggregate structures as well as with changes in the surface morphology induced by MBP.These analyses pertaining to membrane structures will provide a theoretical and experimental basis for the establishment of the myelin membrane modeling system.