Sequence comparison of yeast ATP-binding cassette proteins.
Sequence comparison of yeast ATP-binding cassette proteins.
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DOI：
10.1101/sqb.1995.060.01.034
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
S. Michaelis;C. Berkower
中科院分区：
文献类型：
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作者：
S. Michaelis;C. Berkower
细胞生理学的一个重要方面是离子、营养物质、蛋白质和信号分子在细胞和细胞器膜上的选择性运输，这一过程是由特定的转运蛋白和通道蛋白介导的。在过去的十年中，分子表征表明，这些跨膜蛋白可以分为离散的超家族。一个特定超家族的成员在序列、整体结构和作用机制上都是相似的。这些群体中最大的，也是近年来研究最深入的是atp结合盒（ABC）超家族，也被称为“交通atp酶”，目前包括100多个成员，并继续以快速的速度增长（Higgins 1992； Doige和Ames 1993）。ABC蛋白存在于原核生物和真核生物中，不仅存在于质膜中，也存在于胞内细胞器膜中。由于该超家族的成员在疾病相关过程和正常细胞生理中起着关键作用，ABC蛋白受到了大量关注。医学上值得注意的ABC蛋白包括p -糖蛋白，也称为多药耐药（MDR）蛋白，其在肿瘤细胞中的过度表达使其对多种疏水药物产生耐药性；囊性纤维化跨膜传导调节剂（CFTR），囊性纤维化个体中的离子通道缺陷；以及ALDP和PMP70基因产物，它们分别与过氧化物酶体疾病肾上腺白质营养不良和齐薇格综合征有关。在哺乳动物、昆虫或酵母细胞中执行其他基本生理过程的ABC蛋白包括人类TAPlfFAP2转运蛋白，它将肽泵入内质网（ER）管腔进行抗原呈递；MDR2，一种肝细胞蛋白，在胆汁形成过程中作为一种翻转酶，负责将磷脂酰胆碱穿过肝细胞顶膜；果蝇的白色、棕色和猩红基因产物，它们运输苍蝇眼睛色素的前体；以及输出酵母交配信息素a因子的酿酒酵母STE6蛋白。原核ABC蛋白包括营养摄取渗透酶，如组氨酸渗透酶（HisMPQ）和毒素输出蛋白，如溶血素和大肠杆菌蛋白转运蛋白（分别为HlyB和ColV）。从这几个代表的列表中可以明显看出
A critical aspect of cellular physiology is the selective transport of ions, nutrients, proteins, and signaling molecules across cellular and organellar membranes, processes that are mediated by specific transporter and channel proteins. Over the past decade, molecular characterization has revealed that these transmembrane proteins can be grouped into discrete superfamilies. Members of a particular superfamily are similar in sequence, overall structure, and, presumably, in their mechanism of action. The largest of these groups, and the most intensively studied in recent years, is the ATP-binding cassette (ABC) superfamily, also called the" traffic ATPases," which presently comprises more than 100 members and continues to grow at a rapid rate (Higgins 1992; Doige and Ames 1993). ABC proteins can be found in both prokaryotes and eukaryotes and are present not only in the plasma membrane but also in intracellular organellar membranes.A great deal of attention has been focused on the ABC proteins because members of this superfamily play key roles in disease-related processes as well as in normal cellular physiology. Medically notable ABC proteins include P-glycoprotein, also called the multidrug resistance (MDR) protein, whose overexpression in tumor cells confers resistance to a wide variety of hydrophobic drugs; the cystic fibrosis transmembrane conductance regulator (CFTR), an ion channel defective in individuals with cystic fibrosis; and the ALDP and PMP70 gene products, which have been implicated in the peroxisomal disorders adrenoleukodystrophy and Zellweger syndrome, respectively. ABC proteins that carry out other essential physiological processes in mammalian, insect, or yeast cells include the human TAPlfFAP2 transporter, which pumps peptides into the endoplasmic reticulum (ER) lumen for antigen presentation; MDR2, a liver cell protein that functions as a flippase responsible for moving phosphatidylcholine across the hepatocyte apical membrane during bile formation; the white, brown, and scarlet gene products of Drosophila, which transport precursors of the fly eye pigments; and the Saccharornyces cerevisiae STE6 protein, which exports the yeast mating pheromone a-factor. Prokaryotic ABC proteins include nutrient uptake permeases, such as the histidine permease (HisMPQ), and toxin exporters, such as the hemolysin and coliein transporters (HlyB and ColV, respectively). As is apparent from this list of a few rep-