Apolipoprotein/lipid interactions: studies with synthetic polypeptides.
Apolipoprotein/lipid interactions: studies with synthetic polypeptides.
复制标题
载脂蛋白/脂质相互作用：合成多肽的研究。
DOI：
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发表时间：
1982
期刊：
影响因子：
--
通讯作者：
Antonio M. Gotto
中科院分区：
文献类型：
--
作者：
James T. Sparrow;Antonio M. Gotto
使用肽合成获得载脂蛋白片段，极大地帮助了对血清脂蛋白中发生的复杂相互作用的理解，而这是通过其他方法无法获得的。这些合成材料的脂质结合研究结果总体上支持了 Segrest 等人的两亲性螺旋假说。用于磷脂与载脂蛋白的相互作用。然而，这些相同实验的 CD 结果表明，两亲性螺旋可能没有最初提出的那么大。其他蛋白质结构特征的贡献，例如β-折叠和β-转角与脂质结合的关系尚未得到系统研究。实验数据有力地支持了疏水性对脂质-蛋白质相互作用的重要性。事实上，初步证据表明位于两亲螺旋上配对的酸性和碱性残基下方的疏水残基对于与磷脂的相互作用极其关键。带电残基在结合中的作用尚不清楚，需要进一步研究。前面提到的结构特征的重要性可以通过合成适当取代的肽来阐明。然而，蛋白质-脂质相互作用所涉及的蛋白质结构特征的最终证明必须等待 X 射线衍射分析和详细的 NMR 测量。随着越来越多的肽被合成和研究，作者认为脂质转运和代谢的复杂性将会得到更好的理解。目前正在研究脱辅基蛋白肽片段的表面特性，这可能会导致关于脂蛋白类别之间脱辅基蛋白交换的重要发现。合成肽与控制脂质合成和降解的酶的相互作用增加了对控制这些重要过程的蛋白质-蛋白质和蛋白质-脂质相互作用的理解。合成肽能够加速 apoC-II 缺陷脂蛋白的脂解作用，为使用合成材料治疗这些患者以减少其高甘油三酯血症提供了可能。两亲性螺旋模型的能力为研究疏水性、肽长度、螺旋电位和带电残基在脂质结合中的作用开辟了新的前景。 Pownall 等人的观察。和 Yokayama 等人。这些模型肽的磷脂-胆固醇复合物可以作为 LCAT 的底物，这为进一步研究胆固醇代谢和转运提供了几种令人兴奋的途径。随着这些研究增加了对脂质转运的认识，有可能使用有效的合成脂质结合肽进行治疗干预，以降低血清胆固醇或去除动脉病变中的胆固醇。
The understanding of complex interactions which occur in the serum lipoproteins has been greatly aided by using peptide synthesis to obtain fragments of the apolipoproteins which are unobtainable by other means. The results from lipid-binding studies with these synthetic materials have generally supported the amphipathic helical hypothesis of Segrest et al. for the interaction of phospholipid with the apolipoprotein. However, CD results from these same experiments suggest that the amphipathic helices may not be as large as originally proposed. The contribution of other protein structural features, e.g. beta-sheets and beta-turns, to lipid binding has not been systematically investigated. The importance of hydrophobicity to lipid-protein interaction is strongly supported by the experimental data. Indeed, there is preliminary evidence that the hydrophobic residues positioned beneath the paired acidic and basic residues on the amphipathic helix are extremely critical to the interaction with phospholipid. The role of charged residues in binding is less clear and needs further investigation. The importance of the structural features previously mentioned can be elucidated through the synthesis of appropriately substituted peptides. However, the final proof of the protein structural features involved in protein-lipid interaction must await x-ray diffraction analysis and detailed NMR measurements. As more peptides are synthesized and studied, the authors feel that the complexities of lipid transport and metabolism will be better understood. The surface properties of peptide fragments of the apoproteins are presently being investigated and could lead to important findings on the exchange of apoproteins between lipoprotein classes. The interactions of synthetic peptides with the enzymes which control lipid synthesis and degradation have increased the understanding of protein-protein and protein-lipid interactions which control these important processes. The ability of a synthetic peptide to accelerate lipolysis in an apoC-II deficient lipoprotein offers the potential for treating these patients with synthetic material to reduce their hypertriglyceridemia. The ability to model the amphipathic helix opens new vistas for the study of the role of hydrophobicity, peptide length, helix potential, and charged residues in lipid binding. The observation of Pownall et al. and Yokayama et al. that phospholipid-cholesterol complexes of these model peptides can serve as substrates for LCAT suggests several exciting avenues for further study of cholesterol metabolism and transport. As these studies increase knowledge of lipid transport, the potential exists to intervene therapeutically with potent synthetic lipid-binding peptides to reduce serum cholesterol or to remove cholesterol from arterial lesions.
DOI：
--
发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fukushima,D;Yokoyama,S;Kroon,DJ;Kézdy,FJ;Kaiser,ET
通讯作者：
Kaiser,ET
载脂蛋白 C-I 硝基氧标记或 [13C] 甲基在蛋氨酸 38 处富集的磁共振研究。
影响因子：
2.9
作者：
Chen,TC;Knapp,RD;Rohde,MF;Brainard,JR;GottoJr,AM;Sparrow,JT;Morrisett,JD
通讯作者：
Morrisett,JD