Molecular basis of transport and regulation in the Na+/betaine symporter BetP
Molecular basis of transport and regulation in the Na+/betaine symporter BetP
复制标题
DOI：
10.1038/nature07819
复制
发表时间：
2009-03-05
期刊：
影响因子：
64.8
通讯作者：
Ziegler, Christine
中科院分区：
文献类型：
--
作者：
Ressl, Susanne;van Scheltinga, Anke C. Terwisscha;Ziegler, Christine
渗透调节转运蛋白感知细胞内渗透压，并通过渗透压调节剂的积累对高渗应激作出反应，以恢复正常的水化水平。在这里，我们报告的测定甜菜碱/胆碱/肉毒碱转运蛋白，Na+-耦合的同向转运蛋白BetP从谷氨酸棒杆菌，这是一个非常有效的甜菜碱调节摄取系统的家庭成员的X-射线结构。甘氨酸甜菜碱结合在色氨酸盒中，色氨酸盒从膜的两侧封闭，芳香族侧链排列在运输途径中。BetP具有与三个不相关的Na+-偶联共转运体相同的整体折叠。而这些都是结晶的面向外或面向内的构象，BetP结构揭示了一个独特的中间构象在Na+耦合运输循环。BetP的三聚体结构和三重对称性的断裂由β-敏感C-末端螺旋表明Na+-偶联渗透压转运的调节机制，以抵消渗透胁迫。
Osmoregulated transporters sense intracellular osmotic pressure and respond to hyperosmotic stress by accumulation of osmolytes to restore normal hydration levels. Here we report the determination of the X-ray structure of a member of the family of betaine/choline/carnitine transporters, the Na+-coupled symporter BetP from Corynebacterium glutamicum, which is a highly effective osmoregulated uptake system for glycine betaine. Glycine betaine is bound in a tryptophan box occluded from both sides of the membrane with aromatic side chains lining the transport pathway. BetP has the same overall fold as three unrelated Na+-coupled symporters. Whereas these are crystallized in either the outward-facing or the inward-facing conformation, the BetP structure reveals a unique intermediate conformation in the Na+-coupled transport cycle. The trimeric architecture of BetP and the break in three-fold symmetry by the osmosensing C-terminal helices suggest a regulatory mechanism of Na+-coupled osmolyte transport to counteract osmotic stress.