Interaction of Alzheimer beta-amyloid peptide(1-40) with lipid membranes
Interaction of Alzheimer beta-amyloid peptide(1-40) with lipid membranes
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DOI：
10.1021/bi971843e
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发表时间：
1997-12-02
期刊：
影响因子：
2.9
通讯作者：
Seelig, J
中科院分区：
文献类型：
--
作者：
Terzi, E;Holzemann, G;Seelig, J
β-淀粉样肽β AP（1-40），一种40个氨基酸残基的肽，是阿尔茨海默氏淀粉样沉积物的主要成分之一，β AP（1-40）在水溶液中仅显示有限的溶解度，并且对于C-pep > 10 μ M，经历浓度依赖性的、协同的无规卷曲可逆箭头β-结构转变[Terzi，E.，Halzemann，G.，和Seelig，J.（1995）J. Mol. 252，633-642]。在酸性脂质的存在下，平衡进一步向β-结构聚集体移动，我们现在已经使用圆二色性（CD）光谱、脂质单层以及氘和磷-31固态核磁共振（NMR）表征了脂质-肽相互作用。CD光谱揭示β AP（1-40）和带负电荷的单层囊泡之间的明显相互作用。除了在低脂质与肽（L/P）比下的无规卷曲可逆箭头β结构聚集体平衡之外，在L/P > 55下观察到β结构-> α-螺旋转变。β AP（1-40）在侧压较低（20 mN/m）时可嵌入酸性单分子膜，其嵌入程度随单分子膜中酸性脂质含量的增加而增加。然而，在与双层的脂质堆积密度相当的脂质堆积密度（侧压r 32 mN/m）下，没有观察到β AP（1-40）的插入。用NMR研究了β AP（1-40）存在下的脂质分子结构。将磷脂酰胆碱（PC）在胆碱头基和油酸酰基链的顺式双键上选择性地氘代，并与磷脂酰甘油（PG）混合，磷-31 NMR表明，在所有脂蛋白比下，脂相保持双层结构，氘MMR显示，在添加后，胆碱部分的头基构象或烃链的柔性和有序性没有变化β AP（1-40）。可以得出结论，β A（1-40）静电结合到极性头基区域的外壳上，而不会渗透到极性基团之间。这些数据表明，在带负电荷的膜模板上，β AP（1-40）的五个正电荷的正确排列诱导了螺旋形成的新机制。
The beta-amyloid peptide beta AP(1-40), a 40-amino acid residues peptide, is one of the major components of Alzheimer's amyloid deposits, beta AP(1-40) exhibits only a limited solubility in aqueous solution and undergoes a concentration-dependent, cooperative random coil reversible arrow beta-structure transition for C-pep > 10 mu M [Terzi, E., Halzemann, G., and Seelig, J. (1995) J. Mol. Biol. 252, 633-642]. In the presence of acidic lipid, the equilibrium is shifted further toward beta-structured aggregates, We have now characterized the lipid-peptide interaction using circular dichroism (CD) spectroscopy, lipid monolayers, and deuterium and phosphorus-31 solid-state nuclear magnetic resonance (NMR). CD spectroscopy revealed a distinct interaction between beta AP(1-40) and negatively charged unilamellar vesicles, In addition to the random coil reversible arrow beta-structured aggregate equilibrium at low lipid-to-peptide (L/P) ratios, a beta-structure --> alpha-helix transition was observed at L/P > 55. beta AP(1-40) was found to insert into acidic monolayers provided the lateral pressure was low (20 mN/m), The extent of incorporation increased distinctly with the content of acidic lipid in the monolayer. However, at a lipid packing density equivalent to that of a bilayer (lateral pressure r 32 mN/m), no insertion of beta AP(1-40) was observed, The lipid molecular structure in the presence of beta AP(1-40) was studied with NMR. Phosphatidylcholine (PC) was selectively deuterated at the choline headgroup and at the cis-double bond of the oleic acyl chain and mixed with phosphatidylglycerol (PG), Phosphorus-31 NMR showed that the lipid phase retained the bilayer structure at all lipid-to-protein ratios, Deuterium MMR revealed no change in the headgroup conformation of the choline moiety or in the flexibility and ordering of the hydrocarbon chains upon the addition of beta AP(1-40). It can be concluded that beta A(1-40) binds electrostatically to the outer envelope of the polar headgroup region without penetrating between the polar groups. The data suggest a new mechanism of helix formation induced by the proper alignment of five positive charges of beta AP(1-40) on the negatively charged membrane template.