Structure and mechanism of ABC transporters.
Structure and mechanism of ABC transporters.
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DOI：
10.12703/p7-14
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发表时间：
2015
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影响因子：
--
通讯作者：
Wilkens S
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文献类型：
--
作者：
Wilkens S
所有生物都依赖初级和次级膜运输来提供外部营养物质和去除或隔离不需要的（有毒）化合物。由于细胞分子的化学多样性，蛋白质组的很大一部分致力于通过质膜或亚细胞器膜的主动运输，这并不奇怪。针对化学梯度的运输可以由，例如，与ATP水解相关的自由能变化（一次运输）驱动，或由另一个分子的化学梯度势能（二次运输）促进。主要转运蛋白包括旋转马达ATP酶（F-， A-和v -ATP酶），p型ATP酶和称为“ABC”（ATP结合盒）转运蛋白的一大家族的完整膜蛋白。ABC转运蛋白广泛存在于所有生命形式中，其特征是两个核苷酸结合结构域（NBD）和两个跨膜结构域（TMDs）。NBD上的ATP水解驱动TMD的构象变化，导致细胞内外交替进入，单向通过脂质双分子层运输。所有ABC转运蛋白共有的特征序列或基序是参与核苷酸结合的LSGGQ。输入和输出ABC转运蛋白均存在于细菌中，而大多数真核生物家族成员则在输出方向发挥作用。最近对各种细菌和真核生物ABC转运体的x射线晶体结构测定的进展有助于提高我们对ATP水解驱动的转运机制的理解，但也说明了该家族内部巨大的结构和功能多样性。
All living organisms depend on primary and secondary membrane transport for the supply of external nutrients and removal or sequestration of unwanted (toxic) compounds. Due to the chemical diversity of cellular molecules, it comes as no surprise that a significant part of the proteome is dedicated to the active transport of cargo across the plasma membrane or the membranes of subcellular organelles. Transport against a chemical gradient can be driven by, for example, the free energy change associated with ATP hydrolysis (primary transport), or facilitated by the potential energy of the chemical gradient of another molecule (secondary transport). Primary transporters include the rotary motor ATPases (F-, A-, and V-ATPases), P-type ATPases and a large family of integral membrane proteins referred to as “ABC” (ATP binding cassette) transporters. ABC transporters are widespread in all forms of life and are characterized by two nucleotide-binding domains (NBD) and two transmembrane domains (TMDs). ATP hydrolysis on the NBD drives conformational changes in the TMD, resulting in alternating access from inside and outside of the cell for unidirectional transport across the lipid bilayer. Common to all ABC transporters is a signature sequence or motif, LSGGQ, that is involved in nucleotide binding. Both importing and exporting ABC transporters are found in bacteria, whereas the majority of eukaryotic family members function in the direction of export. Recent progress with the X-ray crystal structure determination of a variety of bacterial and eukaryotic ABC transporters has helped to advance our understanding of the ATP hydrolysis-driven transport mechanism but has also illustrated the large structural and functional diversity within the family.