Structural basis of trans-inhibition in a molybdate/tungstate ABC transporter
Structural basis of trans-inhibition in a molybdate/tungstate ABC transporter
复制标题
DOI：
10.1126/science.1156213
复制
发表时间：
2008-07-11
期刊：
影响因子：
56.9
通讯作者：
Locher, Kaspar P.
中科院分区：
文献类型：
--
作者：
Gerber, Sabina;Comellas-Bigler, Mireia;Locher, Kaspar P.
跨细胞膜转运是由多种膜转运蛋白催化的重要过程。某些转运蛋白的周转率在称为反式抑制的过程中受到其底物的抑制，但其结构基础尚不清楚。我们提出了一个反式抑制状态下的乙酸甲烷八叠球菌的α-/钨酸盐ABC转运蛋白（ModBC）的晶体结构。核苷酸结合亚基的调节结构域紧密接触，并在共享界面处提供两个氧阴离子结合口袋。通过与这些口袋特异性结合，三磷酸腺苷或钨酸盐阻止腺苷三磷酸酶活性，并将转运蛋白锁定在向内的构象中，核苷酸结合结构域的催化基序分离.这种变构效应阻止转运蛋白在面向内和面向外的状态之间切换，从而干扰交替进入和释放机制。
Transport across cellular membranes is an essential process that is catalyzed by diverse membrane transport proteins. The turnover rates of certain transporters are inhibited by their substrates in a process termed trans- inhibition, whose structural basis is poorly understood. We present the crystal structure of a molybdate/ tungstate ABC transporter ( ModBC) from Methanosarcina acetivorans in a trans- inhibited state. The regulatory domains of the nucleotide- binding subunits are in close contact and provide two oxyanion binding pockets at the shared interface. By specifically binding to these pockets, molybdate or tungstate prevent adenosine triphosphatase activity and lock the transporter in an inward- facing conformation, with the catalytic motifs of the nucleotide- binding domains separated. This allosteric effect prevents the transporter from switching between the inward- facing and the outward- facing states, thus interfering with the alternating access and release mechanism.