The E-coli BtuCD structure:: A framework for ABC transporter architecture and mechanism
The E-coli BtuCD structure:: A framework for ABC transporter architecture and mechanism
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DOI：
10.1126/science.1071142
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发表时间：
2002-05-10
期刊：
影响因子：
56.9
通讯作者：
Rees, DC
中科院分区：
文献类型：
--
作者：
Locher, KP;Lee, AT;Rees, DC
ABC转运蛋白是无处不在的膜蛋白，将三磷酸腺苷（ATP）水解与跨细胞膜的各种底物的易位。临床上相关的例子与囊性纤维化以及致病细菌和癌细胞的多药耐药性有关。在这里，我们报告了3.2的晶体结构在3.2埃氏大肠杆菌BTUCD蛋白（一种介导维生素B-12摄取的ABC转运蛋白）分辨率。两个ATP结合盒（BTUD）和两个跨膜亚基（BTUC）彼此紧密接触。这种布置与大肠杆菌脂质Flippase MSBA观察到的布置不同。 BTUC亚基提供了20个跨膜螺旋，这些跨膜螺旋在易位途径周围分组为栅极区域，该易位途径由栅极区域封闭，而BTUD亚基的二聚体排列类似于Rad50 DNA修复酶的ATP结合形式。 BTUC的突出细胞质环形成与ATP结合盒的接触区域，似乎代表了ABC转运蛋白中的保守基序。
The ABC transporters are ubiquitous membrane proteins that couple adenosine triphosphate (ATP) hydrolysis to the translocation of diverse substrates across cell membranes. Clinically relevant examples are associated with cystic fibrosis and with multidrug resistance of pathogenic bacteria and cancer cells. Here, we report the crystal structure at 3.2 angstrom resolution of the Escherichia coli BtuCD protein, an ABC transporter mediating vitamin B-12 uptake. The two ATP-binding cassettes (BtuD) are in close contact with each other, as are the two membrane-spanning subunits (BtuC); this arrangement is distinct from that observed for the E. coli lipid flippase MsbA. The BtuC subunits provide 20 transmembrane helices grouped around a translocation pathway that is closed to the cytoplasm by a gate region whereas the dimer arrangement of the BtuD subunits resembles the ATP-bound form of the Rad50 DNA repair enzyme. A prominent cytoplasmic loop of BtuC forms the contact region with the ATP-binding cassette and appears to represent a conserved motif among the ABC transporters.