Structural Basis for the Counter-Transport Mechanism of a H+/Ca2+ Exchanger
Structural Basis for the Counter-Transport Mechanism of a H+/Ca2+ Exchanger
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DOI：
10.1126/science.1239002
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发表时间：
2013-07-12
期刊：
影响因子：
56.9
通讯作者：
Nureki, Osamu
中科院分区：
文献类型：
--
作者：
Nishizawa, Tomohiro;Kita, Satomi;Nureki, Osamu
Ca2 +/阳离子反向转运蛋白催化Ca2+与各种阳离子的跨生物膜交换，以调节胞质钙水平。最近报道的原核Na +/Ca 2+交换器（NCX_Mj）的结构揭示了其整体结构处于外向状态。在这里，我们报告的晶体结构的H +/Ca2+交换器从古生球菌fulgidus（CAX_Af）在两个代表的向内面向的构象在2.3埃的分辨率。结构表明Ca~（2+）或H~+与阳离子结合位点互斥结合。CAX_Af与NCX_Mj的结构比较显示，第一和第六跨膜螺旋在细胞内外侧交替产生亲水性空腔。结构和功能分析提供了深入了解的机制，向内面向外的状态转换是如何触发的Ca 2+和H+的结合。
Ca2+/cation antiporters catalyze the exchange of Ca2+ with various cations across biological membranes to regulate cytosolic calcium levels. The recently reported structure of a prokaryotic Na+/Ca2+ exchanger (NCX_Mj) revealed its overall architecture in an outward-facing state. Here, we report the crystal structure of a H+/Ca2+ exchanger from Archaeoglobus fulgidus (CAX_Af) in the two representatives of the inward-facing conformation at 2.3 angstrom resolution. The structures suggested Ca2+ or H+ binds to the cation-binding site mutually exclusively. Structural comparison of CAX_Af with NCX_Mj revealed that the first and sixth transmembrane helices alternately create hydrophilic cavities on the intra-and extracellular sides. The structures and functional analyses provide insight into the mechanism of how the inward- to outward-facing state transition is triggered by the Ca2+ and H+ binding.