Division of Structural Biology and Biochemistry, School of Biological Sciences, Nanyang Technological University, Singapore 637551, Republic of Singapore.
Proc Natl Acad Sci U S A. 2012 Nov 6;109(45):18459-64. doi: 10.1073/pnas.1210076109. Epub 2012 Oct 22.
Despite the importance of Mg(2+) for numerous cellular activities, the mechanisms underlying its import and homeostasis are poorly understood. The CorA family is ubiquitous and is primarily responsible for Mg(2+) transport. However, the key questions-such as, the ion selectivity, the transport pathway, and the gating mechanism-have remained unanswered for this protein family. We present a 3.2 Å resolution structure of the archaeal CorA from Methanocaldococcus jannaschii, which is a unique complete structure of a CorA protein and reveals the organization of the selectivity filter, which is composed of the signature motif of this family. The structure reveals that polar residues facing the channel coordinate a partially hydrated Mg(2+) during the transport. Based on these findings, we propose a unique gating mechanism involving a helical turn upon the binding of Mg(2+) to the regulatory intracellular binding sites, and thus converting a polar ion passage into a narrow hydrophobic pore. Because the amino acids involved in the uptake, transport, and gating are all conserved within the entire CorA family, we believe this mechanism is general for the whole family including the eukaryotic homologs.
尽管镁离子对于许多细胞活动都非常重要，但人们对其摄取和稳态的机制知之甚少。CorA 家族普遍存在，主要负责镁离子的运输。然而，对于这种蛋白质家族，一些关键问题，如离子选择性、运输途径和门控机制，仍然没有得到解答。我们展示了来自产甲烷球菌的古菌 CorA 的 3.2 Å 分辨率结构，这是 CorA 蛋白的独特完整结构，揭示了选择性过滤器的组织，该选择性过滤器由该家族的特征基序组成。该结构表明，通道中朝向通道的极性残基在运输过程中与部分水合的镁离子配位。基于这些发现，我们提出了一个独特的门控机制，涉及到结合镁离子到调节细胞内结合位点时的螺旋转弯，从而将极性离子通道转换为狭窄的疏水性孔。由于参与摄取、运输和门控的氨基酸在整个 CorA 家族中都是保守的，我们相信这个机制对于整个家族，包括真核同源物，都是通用的。
