Tripod Amphiphiles for Membrane Protein Manipulation.

Tripod Amphiphiles for Membrane Protein Manipulation.
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DOI:
10.1039/b915162c
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发表时间:
2010
影响因子:
--
通讯作者:
Gellman SH
Gellman SH
中科院分区:
生物3区
文献类型:
--
作者:
Chae PS;Laible PD;Gellman SH

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整合膜蛋白(Imps)是细胞与环境之间传递物质和信息的重要生物成分。事实证明,许多小鬼很难分离和研究。关于这类蛋白质的高分辨率结构信息有限,主要是因为很难产生保持天然折叠和活性的这类蛋白质的可溶性形式,以及很难从这种制剂中产生高质量的晶体。分离的IMP通常不溶于水溶液,这一特性源于疏水表面的大片,这是与脂质双层核心良好相互作用所必需的。洗涤剂通常是IMP增溶所必需的:洗涤剂分子的疏水片段聚集在疏水蛋白质表面并将其与水隔绝。洗涤剂在膜蛋白操作中发挥的关键作用,以及许多IMP对现有洗涤剂的增溶和/或结晶具有顽固性的事实,表明探索用于这些目的的新型两亲性是有价值的。这篇综述是关于我们开发一类新的有机分子的长期努力的进展报告,这些有机分子统称为“三脚型两亲性分子”,旨在作为膜蛋白操作的传统洗涤剂的替代品。这项研究的一个长期目标是确定促进IMP结晶的新型两亲性化合物。这篇综述应该有助于向有机化学家介绍一个重要的生化需求,也许还会启发解决这个问题的新方法。
Integral membrane proteins (IMPs) are crucial biological components, mediating the transfer of material and information between cells and their environment. Many IMPs have proven to be difficult to isolate and study. High-resolution structural information on this class of proteins is limited, largely because of difficulties in generating soluble forms of such proteins that retain native folding and activity, and difficulties in generating high-quality crystals from such preparations. Isolated IMPs typically do not dissolve in aqueous solution, a property that arises from the large patches of hydrophobic surface necessary for favorable interactions with the core of a lipid bilayer. Detergents are generally required for IMP solubilization: hydrophobic segments of detergent molecules cluster around and shield from water the hydrophobic protein surfaces. The critical role played by detergents in membrane protein manipulation, and the fact that many IMPs are recalcitrant to solubilization and/or crystallization with currently available detergents, suggest that it should be valuable to explore new types of amphiphiles for these purposes. This review constitutes a progress report on our long-term effort to develop a new class of organic molecules, collectively designated “tripod amphiphiles,” that are intended as alternatives to conventional detergents for membrane protein manipulation. One long-range goal of this research is to identify new types of amphiphiles that facilitate IMP crystallization. This review should help introduce an important biochemical need to organic chemists, and perhaps inspire new approaches to the problem.
DOI: 10.1016/0014-5793(78)80427-x
发表时间: 1978-01-01
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影响因子: 3.5
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