Structures and models of transporter proteins
Structures and models of transporter proteins
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DOI：
10.1124/jpet.103.059972
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发表时间：
2004-06-01
影响因子：
3.5
通讯作者：
Ravna, AW
中科院分区：
文献类型：
--
作者：
Dahl, SG;Sylte, I;Ravna, AW
生物膜上的转运蛋白可分为通道和载体。通道作为选择性孔起作用，其响应于化学或电生理刺激而打开，允许溶质沿着电化学梯度移动。活性载体蛋白质利用能量产生过程逆着浓度梯度转移底物。次级主动转运蛋白利用溶质沿浓度梯度的移动来驱动另一种底物跨膜移位。ATP结合盒（ABC）转运蛋白将三磷酸腺苷（ATP）的水解与各种底物跨细胞膜的转运偶联。高分辨率的三维结构，现在已经报道了从X射线晶体学研究的六种不同的转运蛋白，包括两个ATP结合盒从许多以前的生化和生物学研究，并阐明其功能机制。所有这些转运蛋白都具有跨膜结构域的α-螺旋结构，如许多先前的研究所建议的，并且一些螺旋具有扭结和弯曲的不规则形状。这些晶体结构一起证明了转运蛋白的大的灵活性，并且在底物易位过程中发生了大量的移动，这在一定程度上可以将活性载体与通道蛋白区分开来。这些结构和膜蛋白的其他低分辨率结构已作为构建三维蛋白质模型的基础，这些模型提供了对功能机制和分子结构的深入了解，并能够制定关于转运蛋白结构和功能的新假设，这些假设可以通过实验验证。
Transporter proteins in biological membranes may be divided into channels and carriers. Channels function as selective pores that open in response to a chemical or electrophysiological stimulus, allowing movement of a solute down an electrochemical gradient. Active carrier proteins use an energy producing process to translocate a substrate against a concentration gradient. Secondary active transporters use the movement of a solute down a concentration gradient to drive the translocation of another substrate across a membrane. ATP-binding cassette (ABC) transporters couple hydrolysis of adenosine triphosphate (ATP) to the translocation of various substrates across cell membranes. High-resolution three-dimensional structures have now been reported from X-ray crystallographic studies of six different transporters, including two ATP-binding cassette from many previous biochemical and biological studies and shed new light on their functional mechanisms. All these transporters have a-helical structures of the membrane-spanning domains, as suggested from many previous studies, and some of the helices have irregular shapes with kinks and bends. Together these crystal structures demonstrate the large flexibility of transporter proteins and that substantial movements take place during the substrate translocation process, which to a certain extent may distinguish active carriers from channel proteins. These structures and other low-resolution structures of membrane proteins have served as a basis for construction of three-dimensional protein models that have provided insight into functional mechanisms and molecular structures and enabled formulation of new hypotheses regarding transporter structure and function, which may be experimentally validated.