The ins and outs of vesicular monoamine transporters.
The ins and outs of vesicular monoamine transporters.
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DOI：
10.1085/jgp.201711980
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发表时间：
2018-05-07
期刊：
影响因子：
--
通讯作者：
Schuldiner S
中科院分区：
文献类型：
--
作者：
Yaffe D;Forrest LR;Schuldiner S
Yaffe等人回顾了结构引导的研究，这些研究深入了解了VMAT的质子-单胺反向转运机制。 H+偶联囊泡单胺转运体（VMAT）是生命所必需的转运体。VMAT介导单胺5-羟色胺、多巴胺、去甲肾上腺素和组胺从神经元细胞质包装到突触前囊泡中，这是调节神经递质释放的关键步骤。然而，由于缺乏高分辨率的结构数据，对VMAT功能机制的详细了解受到限制。近年来，一系列的同源性模型指导下的研究已经揭示了VMAT功能的重要见解，确定残基，有助于结合位点和运输循环中的特定步骤。此外，为了表征底物和偶联离子结合后发生的构象转变，我们利用了VMAT独特而强大的药理学以及影响蛋白质构象平衡并将其向定义构象转变的突变体。这使我们能够确定一个重要的作用，质子梯度驱动的转变，从内腔面向细胞质面向构象。
Yaffe et al. review structure-guided studies that have provided insight into the mechanism of proton-monoamine antiport by VMATs. The H+-coupled vesicular monoamine transporter (VMAT) is a transporter essential for life. VMAT mediates packaging of the monoamines serotonin, dopamine, norepinephrine, and histamine from the neuronal cytoplasm into presynaptic vesicles, which is a key step in the regulated release of neurotransmitters. However, a detailed understanding of the mechanism of VMAT function has been limited by the lack of availability of high-resolution structural data. In recent years, a series of studies guided by homology models has revealed significant insights into VMAT function, identifying residues that contribute to the binding site and to specific steps in the transport cycle. Moreover, to characterize the conformational transitions that occur upon binding of the substrate and coupling ion, we have taken advantage of the unique and powerful pharmacology of VMAT as well as of mutants that affect the conformational equilibrium of the protein and shift it toward defined conformations. This has allowed us to identify an important role for the proton gradient in driving a shift from lumen-facing to cytoplasm-facing conformations.
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影响因子：
5.7
作者：
Fowler, Philip W.;Orwick-Rydmark, Marcella;Radestock, Sebastian;Solcan, Nicolae;Dijkman, Patricia M.;Lyons, Joseph A.;Kwok, Jane;Caffrey, Martin;Watts, Anthony;Forrest, Lucy R.;Newstead, Simon
通讯作者：
Newstead, Simon
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
DOI：
10.1073/pnas.0804659105
发表时间：
2008-07-29
影响因子：
11.1
作者：
Forrest, Lucy R.;Zhang, Yuan-Wei;Rudnick, Gary
通讯作者：
Rudnick, Gary
非竞争性ibogaine抑制5-羟色胺和多巴胺转运蛋白的机械基础。
DOI：
10.1074/jbc.m112.343681
发表时间：
2012-05-25
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bulling S;Schicker K;Zhang YW;Steinkellner T;Stockner T;Gruber CW;Boehm S;Freissmuth M;Rudnick G;Sitte HH;Sandtner W
通讯作者：
Sandtner W
影响因子：
16
作者：
Fluman N;Ryan CM;Whitelegge JP;Bibi E
通讯作者：
Bibi E