Molecular genetic and biochemical approaches for defining lipid-dependent membrane protein folding.
Molecular genetic and biochemical approaches for defining lipid-dependent membrane protein folding.
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DOI：
10.1016/j.bbamem.2011.09.013
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发表时间：
2012-04
影响因子：
3.4
通讯作者：
Bogdanov, Mikhail
中科院分区：
文献类型：
--
作者：
Dowhan, William;Bogdanov, Mikhail
我们提供了一个概述的脂质依赖性多位膜蛋白折叠和拓扑发生。采用大肠杆菌细胞，其中特定的脂质可以消除，取代，严格滴定或控制膜蛋白合成和组装过程中的时间，确定了这一过程的脂质依赖性。次级转运蛋白乳糖通透酶（LacY）被用来建立脂质依赖性影响蛋白质结构域折叠，蛋白质跨膜结构域（TM）的方向和功能的分子基础的一般原则。这些原则，然后扩展到其他几个二级转运蛋白的E。杆菌描述了用于跟踪蛋白质结构域的正确构象组织和蛋白质TM在整个细胞和膜中的拓扑组织的方法。LacY的膜外结构域的正确折叠对于能量依赖性上坡运输功能至关重要，这取决于充当非蛋白质分子伴侣的特定脂质。正确的TM拓扑结构依赖于膜蛋白质的细胞质表面之间的电荷相互作用和由脂质头部基团定义的膜表面净电荷的适当平衡。新生蛋白质链和易位子之间的短程相互作用是必要的，但不足以建立最终的拓扑结构。从易位子释放后，脂质头部基团和新生蛋白质链之间的短程相互作用，蛋白质疏水结构域到膜双分子层的分区，和蛋白质内的长程相互作用决定性地驱动最终的膜蛋白组织。鉴于整个自然界中膜脂质组成的多样性，人们很容易推测，在进化过程中，蛋白质和脂质的物理和化学性质在膜系统的脂质环境中共同进化，其中两者相互依赖于彼此以实现蛋白质的功能组织。
We provide an overview of lipid-dependent polytopic membrane protein folding and topogenesis. Lipid dependence of this process was determined by employing Escherichia coli cells in which specific lipids can be eliminated, substituted, tightly titrated or controlled temporally during membrane protein synthesis and assembly. The secondary transport protein lactose permease (LacY) was used to establish general principles underlying the molecular basis of lipid-dependent effects on protein domain folding, protein transmembrane domain (TM) orientation, and function. These principles were then extended to several other secondary transport proteins of E. coli. The methods used to follow proper conformational organization of protein domains and the topological organization of protein TMs in whole cells and membranes are described. The proper folding of an extramembrane domain of LacY that is crucial for energy dependent uphill transport function depends on specific lipids acting as non-protein molecular chaperones. Correct TM topogenesis is dependent on charge interactions between the cytoplasmic surface of membrane proteins and a proper balance of the membrane surface net charge defined by the lipid head groups. Short-range interactions between the nascent protein chain and the translocon are necessary but not sufficient for establishment of final topology. After release from the translocon short-range interactions between lipid head groups and the nascent protein chain, partitioning of protein hydrophobic domains into the membrane bilayer, and long–range interactions within the protein thermodynamically drive final membrane protein organization. Given the diversity of membrane lipid compositions throughout nature, it is tempting to speculate that during the course of evolution the physical and chemical properties of proteins and lipids have co-evolved in the context of the lipid environment of membrane systems in which both are mutually depend on each other for functional organization of proteins.
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影响因子：
4.8
作者：
BOGDANOV, M;DOWHAN, W
通讯作者：
DOWHAN, W
影响因子：
8
作者：
Gbaguidi, B.;Hakizimana, P.;Ruysschaert, J.-M.
通讯作者：
Ruysschaert, J.-M.
影响因子：
2.9
作者：
Frillingos, S;Wu, JH;Kaback, HR
通讯作者：
Kaback, HR
影响因子：
4.8
作者：
Bogdanov, M;Umeda, M;Dowhan, W
通讯作者：
Dowhan, W
影响因子：
11.4
作者：
DUNLOP, J;JONES, PC;FINBOW, ME
通讯作者：
FINBOW, ME