生物谷報(bào)道：日本科學(xué)家報(bào)告說，他們通過分析鎂轉(zhuǎn)運(yùn)體的立體結(jié)構(gòu),，解開了機(jī)體維持鎂元素平衡的機(jī)制,，這將有助于治療心肌梗塞等心臟疾病。
日本科學(xué)技術(shù)振興機(jī)構(gòu)和東京工業(yè)大學(xué)日前發(fā)表聯(lián)合公報(bào)說,，鎂對(duì)所有生命體來說都是不可缺少的元素,，缺鎂是引發(fā)心肌梗塞等缺血性心臟病的原因之一，但是過度攝取鎂對(duì)機(jī)體反而有害,。機(jī)體如何維持鎂平衡,，是科學(xué)界長(zhǎng)期沒有解決的一個(gè)問題。
在此次研究中,，研究人員利用Ｘ射線結(jié)晶構(gòu)造分析方法,，確定了在鎂存在的條件下，細(xì)胞膜上的鎂轉(zhuǎn)運(yùn)體ＭｇｔＥ的立體結(jié)構(gòu),。鎂轉(zhuǎn)運(yùn)體ＭｇｔＥ可以把細(xì)胞外的鎂離子運(yùn)送到細(xì)胞內(nèi),。
分析顯示，ＭｇｔＥ轉(zhuǎn)運(yùn)體上存在鎂進(jìn)出細(xì)胞的通道,。ＭｇｔＥ能夠感知細(xì)胞內(nèi)鎂濃度的變化,，然后根據(jù)情況關(guān)閉或打開通道，從而維持機(jī)體的鎂平衡,。
相關(guān)論文已刊登于最新一期英國(guó)《自然》雜志網(wǎng)絡(luò)版上,。（新華網(wǎng)）
原始出處:
Nature advance online publication 15 August 2007 | doi:10.1038/nature06093; Received 18 April 2007; Accepted 16 July 2007; Published online 15 August 2007
Crystal structure of the MgtE Mg2+ transporter
Motoyuki Hattori1, Yoshiki Tanaka1, Shuya Fukai2, Ryuichiro Ishitani1 & Osamu Nureki1,3
Department of Biological Information, Graduate School of Bioscience and Biotechnology,
Center for Biological Resources and Informatics, Tokyo Institute of Technology, 4259 Nagatsuta-cho, Midori-ku, Yokohama-shi, Kanagawa 226-8501, Japan
SORST, JST, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
Correspondence to: Osamu Nureki1,3 Correspondence and requests for materials should be addressed to O.N. (Email: [email protected]).
The magnesium ion Mg2+ is a vital element involved in numerous physiological processes. Mg2+ has the largest hydrated radius among all cations, whereas its ionic radius is the smallest. It remains obscure how Mg2+ transporters selectively recognize and dehydrate the large, fully hydrated Mg2+ cation for transport1. Recently the crystal structures of the CorA Mg2+ transporter2, 3, 4, 5 were reported6, 7, 8. The MgtE family of Mg2+ transporters is ubiquitously distributed in all phylogenetic domains9, 10, 11, and human homologues have been functionally characterized and suggested to be involved in magnesium homeostasis12, 13, 14. However, the MgtE transporters have not been thoroughly characterized. Here we determine the crystal structures of the full-length Thermus thermophilus MgtE at 3.5 Å resolution, and of the cytosolic domain in the presence and absence of Mg2+ at 2.3 Å and 3.9 Å resolutions, respectively. The transporter adopts a homodimeric architecture, consisting of the carboxy-terminal five transmembrane domains and the amino-terminal cytosolic domains, which are composed of the superhelical N domain and tandemly repeated cystathionine--synthase domains. A solvent-accessible pore nearly traverses the transmembrane domains, with one potential Mg2+ bound to the conserved Asp 432 within the pore. The transmembrane (TM)5 helices from both subunits close the pore through interactions with the 'connecting helices', which connect the cystathionine--synthase and transmembrane domains. Four putative Mg2+ ions are bound at the interface between the connecting helices and the other domains, and this may lock the closed conformation of the pore. A structural comparison of the two states of the cytosolic domains showed the Mg2+-dependent movement of the connecting helices, which might reorganize the transmembrane helices to open the pore. These findings suggest a homeostasis mechanism, in which Mg2+ bound between cytosolic domains regulates Mg2+ flux by sensing the intracellular Mg2+ concentration. Whether this presumed regulation controls gating of an ion channel or opening of a secondary active transporter remains to be determined.
