Maleš Petra, Brkljača Zlatko, Crnolatac Ivo, Petrov Dražen, Bakarić Danijela
Division for Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia.
Institute of Molecular Modeling and Simulation, University of Natural Resources and Life Sciences, 1180 Vienna, Austria.
Membranes (Basel). 2024 Jan 4;14(1):15. doi: 10.3390/membranes14010015.
The dense packing of opposite cytoplasmic surfaces of the lipid-enriched myelin membrane, responsible for the proper saltatory conduction of nerve impulses through axons, is ensured by the adhesive properties of myelin basic protein (MBP). Although preferentially interacting with negatively charged phosphatidylserine (PS) lipids, as an intrinsically disordered protein, it can easily adapt its shape to its immediate environment and thus adsorb to domains made of zwitterionic phosphatidylcholine (PC) lipids. As the molecular-level interaction pattern between MBP and PC lipid membranes suffers from scarce characterization, an experimental and computational study of multilamellar liposomes (MLVs) composed of 1,2-dipalmitoyl--glycero-3-phosphocholine (DPPC) in the presence of bovine MBP is presented here. Calorimetric and temperature-dependent UV-Vis measurements identified DPPC pretransition temperature () and calorimetric enthalpy (Δ) as the physicochemical parameters most responsive to the presence of MBP. Besides suggesting an increase in β-sheet fractions of structured MBP segments as DPPC lipids undergo from the gel (20 °C) to the fluid (50 °C) phase, FTIR spectra unraveled the significant contribution of lysine (Lys) residues in the adsorption pattern, especially when DPPC is in the fluid (50 °C) phase. In addition to highlighting the importance of Lys residues in the MBP adsorption on DPPC lipid bilayer, employing salt bridges (SBs) and hydrogen bonds (HBs), MD data suggest the crucial importance of the orientation of MBP with respect to the surface of the DPPC lipid bilayer.
富含脂质的髓鞘膜相对细胞质表面的紧密堆积，负责神经冲动通过轴突的正常跳跃传导，这是由髓鞘碱性蛋白（MBP）的黏附特性来确保的。尽管MBP优先与带负电荷的磷脂酰丝氨酸（PS）脂质相互作用，但作为一种内在无序的蛋白质，它可以很容易地使其形状适应其周围环境，从而吸附到由两性离子磷脂酰胆碱（PC）脂质构成的区域。由于MBP与PC脂质膜之间的分子水平相互作用模式缺乏充分表征，本文介绍了在牛MBP存在下由1,2 - 二棕榈酰 - sn -甘油 - 3 - 磷酸胆碱（DPPC）组成的多层脂质体（MLV）的实验和计算研究。量热法和温度依赖性紫外 - 可见光谱测量确定DPPC的预转变温度（）和量热焓（Δ）是对MBP的存在最敏感的物理化学参数。除了表明随着DPPC脂质从凝胶相（20°C）转变为流体相（50°C），结构化MBP片段的β - 折叠部分增加外，傅里叶变换红外光谱揭示了赖氨酸（Lys）残基在吸附模式中的重要贡献，特别是当DPPC处于流体相（50°C）时。除了强调Lys残基在MBP吸附到DPPC脂质双层中的重要性，利用盐桥（SBs）和氢键（HBs），分子动力学（MD）数据表明MBP相对于DPPC脂质双层表面的取向至关重要。
