Hung L W, Wang I X, Nikaido K, Liu P Q, Ames G F, Kim S H
E. O. Lawrence Berkeley National Laboratory, University of California at Berkeley, 94720, USA.
Nature. 1998 Dec 17;396(6712):703-7. doi: 10.1038/25393.
ABC transporters (also known as traffic ATPases) form a large family of proteins responsible for the translocation of a variety of compounds across membranes of both prokaryotes and eukaryotes. The recently completed Escherichia coli genome sequence revealed that the largest family of paralogous E. coli proteins is composed of ABC transporters. Many eukaryotic proteins of medical significance belong to this family, such as the cystic fibrosis transmembrane conductance regulator (CFTR), the P-glycoprotein (or multidrug-resistance protein) and the heterodimeric transporter associated with antigen processing (Tap1-Tap2). Here we report the crystal structure at 1.5 A resolution of HisP, the ATP-binding subunit of the histidine permease, which is an ABC transporter from Salmonella typhimurium. We correlate the details of this structure with the biochemical, genetic and biophysical properties of the wild-type and several mutant HisP proteins. The structure provides a basis for understanding properties of ABC transporters and of defective CFTR proteins.
ABC转运蛋白（也称为转运ATP酶）构成了一个庞大的蛋白质家族，负责多种化合物在原核生物和真核生物膜上的转运。最近完成的大肠杆菌基因组序列显示，大肠杆菌中最大的旁系同源蛋白家族由ABC转运蛋白组成。许多具有医学意义的真核蛋白都属于这个家族，如囊性纤维化跨膜传导调节因子（CFTR）、P-糖蛋白（或多药耐药蛋白）以及与抗原加工相关的异二聚体转运蛋白（Tap1-Tap2）。本文报道了鼠伤寒沙门氏菌的组氨酸通透酶的ATP结合亚基HisP的1.5埃分辨率晶体结构。我们将该结构的细节与野生型和几种突变型HisP蛋白的生化、遗传和生物物理特性相关联。该结构为理解ABC转运蛋白和有缺陷的CFTR蛋白的特性提供了基础。
