Structural basis for the Mg(2+) recognition and regulation of the CorC Mg(2+) transporter.

Structural basis for the Mg(2+) recognition and regulation of the CorC Mg(2+) transporter.
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Corc镁离子转运蛋白识别和调控镁离子的结构基础。

DOI:
10.1126/sciadv.abe6140
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发表时间:
2021-03
期刊:
影响因子:
13.6
通讯作者:
Hattori M
Hattori M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Huang Y;Jin F;Funato Y;Xu Z;Zhu W;Wang J;Sun M;Zhao Y;Yu Y;Miki H;Hattori M

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CorC Mg2+转运蛋白的晶体结构揭示了与遗传疾病相关的独特的Mg2+结合位点。 CNNM/CorC 家族蛋白是广泛分布于生命各个领域的 Mg2+ 转运蛋白。在细菌中,CorC 与病原微生物的生存有关。在人类中,CNNM 蛋白参与各种生物事件,例如 Mg2+ 的身体吸收/重吸收和遗传性疾病。在这里,我们确定了 Mg2+ 结合的 CorC TM 域二聚体的晶体结构。每个原聚体都有一个带有完全脱水的 Mg2+ 离子的 Mg2+ 结合位点。 Mg2+结合位点的残基在人类CNNM2和CNNM4中都是严格保守的,其中许多残基与遗传疾病有关。此外,我们还确定了包含其调节性 ATP 结合域的 CorC 细胞质区域的结构。结构和功能分析的结合不仅揭示了 TM 和细胞质结构域之间的潜在界面,而且还表明 ATP 结合对于 CorC 的 Mg2+ 输出活性很重要。
Crystal structures of the CorC Mg2+ transporter revealed the unique Mg2+ binding site associated with genetic diseases. The CNNM/CorC family proteins are Mg2+ transporters that are widely distributed in all domains of life. In bacteria, CorC has been implicated in the survival of pathogenic microorganisms. In humans, CNNM proteins are involved in various biological events, such as body absorption/reabsorption of Mg2+ and genetic disorders. Here, we determined the crystal structure of the Mg2+-bound CorC TM domain dimer. Each protomer has a single Mg2+ binding site with a fully dehydrated Mg2+ ion. The residues at the Mg2+ binding site are strictly conserved in both human CNNM2 and CNNM4, and many of these residues are associated with genetic diseases. Furthermore, we determined the structures of the CorC cytoplasmic region containing its regulatory ATP-binding domain. A combination of structural and functional analyses not only revealed the potential interface between the TM and cytoplasmic domains but also showed that ATP binding is important for the Mg2+ export activity of CorC.
DOI: 10.1038/onc.2014.33
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