The high-affinity E. coli methionine ABC transporter: structure and allosteric regulation.
The high-affinity E. coli methionine ABC transporter: structure and allosteric regulation.
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DOI：
10.1126/science.1157987
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发表时间：
2008-07-11
期刊：
影响因子：
--
通讯作者：
Rees DC
中科院分区：
文献类型：
--
作者：
Kadaba NS;Kaiser JT;Johnson E;Lee A;Rees DC
高亲和力大肠杆菌MetNI蛋氨酸摄取转运蛋白，ATP结合盒（ABC）家族的成员，的晶体结构已解决了3.7 μ m的分辨率。MetNI的总体结构揭示了ATP酶MetN的两个拷贝与跨膜结构域MetI的两个拷贝的复合体，其中转运蛋白采用向内的构象，表现出广泛分离的核苷酸结合结构域。每个MetI亚基围绕五个跨膜螺旋的核心组织，所述跨膜螺旋对应于在MMPodBC和麦芽糖MalFGK ABC转运蛋白的较大跨膜亚基中观察到的螺旋的子集。除了ABC家族的保守核苷酸结合结构域之外，MetN还含有属于ACT结构域家族的C-末端延伸，该ACT结构域家族先前被提出代表保守的调节结合折叠。这些结构域将核苷酸结合结构域分开，并且会干扰ATP结合和水解所需的它们的缔合。甲硫氨酸结合二聚化的C-末端结构域，并显示抑制ATP酶活性。这些观察结果与在转运活性水平下操作的变构调节机制一致，其中增加的转运配体的细胞内水平稳定MetNI的面向内的ATP酶失活状态以抑制配体进一步易位到细胞中。
The crystal structure of the high affinity Escherichia coli MetNI methionine uptake transporter, a member of the ATP Binding Cassette (ABC) family, has been solved to 3.7 Å resolution. The overall architecture of MetNI reveals two copies of the ATPase MetN in complex with two copies of the transmembrane domain MetI, with the transporter adopting an inward-facing conformation exhibiting widely separated nucleotide binding domains. Each MetI subunit is organized around a core of five transmembrane helices that correspond to a subset of the helices observed in the larger membrane spanning subunits of the molybdate ModBC and maltose MalFGK ABC transporters. In addition to the conserved nucleotide binding domain of the ABC family, MetN contains a C-terminal extension belonging to the ACT-domain family previously proposed to represent a conserved regulatory binding fold. These domains separate the nucleotide binding domains and would interfere with their association required for ATP binding and hydrolysis. Methionine binds to the dimerized C-terminal domain and is shown to inhibit ATPase activity. These observations are consistent with an allosteric regulatory mechanism operating at the level of transport activity, where increased intracellular levels of the transported ligand stabilize an inward-facing, ATPase-inactive state of MetNI to inhibit further ligand translocation into the cell.
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