Conformationally Preorganized Diastereomeric Norbornane-Based Maltosides for Membrane Protein Study: Implications of Detergent Kink for Micellar Properties.
Conformationally Preorganized Diastereomeric Norbornane-Based Maltosides for Membrane Protein Study: Implications of Detergent Kink for Micellar Properties.
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DOI：
10.1021/jacs.6b11997
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发表时间：
2017-03-01
影响因子：
15
通讯作者：
Chae PS
中科院分区：
文献类型：
--
作者：
Das M;Du Y;Ribeiro O;Hariharan P;Mortensen JS;Patra D;Skiniotis G;Loland CJ;Guan L;Kobilka BK;Byrne B;Chae PS
去污剂是研究膜蛋白功能和结构的重要工具。然而，传统的洗涤剂在其范围和用途上是有限的，特别是对真核膜蛋白。因此，有主要的努力，以开发新的两亲剂具有增强的性质。本文制备了一类具有预组织构象的新型非对映异构体，称为降冰片基麦芽糖苷（NBMs），并对其溶解和稳定膜蛋白的能力进行了评估。与n-十二烷基-β-d-麦芽糖苷（DDM）相比，具有代表性的NBMs对所有被测试的膜蛋白表现出增强的行为。单个NBMs的功效取决于整体洗涤剂的形状和烷基链的长度。具体来说，亲脂区没有扭结的NBMs比有扭结的NBMs赋予蛋白质更大的稳定性。此外，长烷基链NBMs在稳定膜蛋白方面普遍优于短烷基链NBMs。此外，使用一种性能良好的NBM使我们能够在电子显微镜下获得明显的稳定性和清晰的膜蛋白复合物的可视化。因此，这项研究不仅描述了具有增强蛋白质稳定特性的新型麦芽糖苷洗涤剂，而且还表明，总体洗涤剂几何形状在决定膜蛋白稳定性方面具有重要作用。值得注意的是，这是第一次系统地研究洗涤剂扭结对胶束性质和相关膜蛋白稳定性的影响。
Detergents are essential tools for functional and structural studies of membrane proteins. However, conventional detergents are limited in their scope and utility, particularly for eukaryotic membrane proteins. Thus, there are major efforts to develop new amphipathic agents with enhanced properties. Here, a novel class of diastereomeric agents with a preorganized conformation, designated norbornane-based maltosides (NBMs), were prepared and evaluated for their ability to solubilize and stabilize membrane proteins. Representative NBMs displayed enhanced behaviors compared to n-dodecyl-β-d-maltoside (DDM) for all membrane proteins tested. Efficacy of the individual NBMs varied depending on the overall detergent shape and alkyl chain length. Specifically, NBMs with no kink in the lipophilic region conferred greater stability to the proteins than NBMs with a kink. In addition, long alkyl chain NBMs were generally better at stabilizing membrane proteins than short alkyl chain agents. Furthermore, use of one well-behaving NBM enabled us to attain a marked stabilization and clear visualization of a challenging membrane protein complex using electron microscopy. Thus, this study not only describes novel maltoside detergents with enhanced protein-stabilizing properties but also suggests that overall detergent geometry has an important role in determining membrane protein stability. Notably, this is the first systematic study on the effect of detergent kinking on micellar properties and associated membrane protein stability.
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MelB 的基于结构的 Na(+)/蜜二糖同向机制。
影响因子：
16.6
作者：
Ethayathulla, Abdul S.;Yousef, Mohammad S.;Amin, Anowarul;Leblanc, Gerard;Kaback, H. Ronald;Guan, Lan
通讯作者：
Guan, Lan
影响因子：
2.9
作者：
Amin, Anowarul;Hariharan, Parameswaran;Guan, Lan
通讯作者：
Guan, Lan
影响因子：
64.8
作者：
Granier, Sebastien;Manglik, Aashish;Kruse, Andrew C.;Kobilka, Tong Sun;Thian, Foon Sun;Weis, William I.;Kobilka, Brian K.
通讯作者：
Kobilka, Brian K.
用于膜蛋白稳定的串联面两亲物。
影响因子：
15
作者：
Chae PS;Gotfryd K;Pacyna J;Miercke LJ;Rasmussen SG;Robbins RA;Rana RR;Loland CJ;Kobilka B;Stroud R;Byrne B;Gether U;Gellman SH
通讯作者：
Gellman SH
影响因子：
--
作者：
Chae PS;Laible PD;Gellman SH
通讯作者：
Gellman SH