Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca(2+)/H(+) antiporter.
Leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) forms a Ca(2+)/H(+) antiporter.
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含有跨膜蛋白 1 (LETM1) 的亮氨酸拉链-EF-手形成 Ca2/H 逆向转运蛋白
DOI:
10.1038/srep34174
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发表时间:
2016-09-27
影响因子:
4.6
通讯作者:
Shen Y
中科院分区:
文献类型:
--
作者:
Shao J;Fu Z;Ji Y;Guan X;Guo S;Ding Z;Yang X;Cong Y;Shen Y
Leucine zipper-EF-hand-containing transmembrane protein1 (LETM1) is located in the mitochondrial inner membrane and is defective in Wolf-Hirschhorn syndrome. LETM1 contains only one transmembrane helix, but it behaves as a putative transporter. Our data shows that LETM1 knockdown or overexpression robustly increases or decreases mitochondrial Ca2+ level in HeLa cells, respectively. Also the residue Glu221 of mouse LETM1 is identified to be necessary for Ca2+ flux. The mutation of Glu221 to glutamine abolishes the Ca2+-transport activity of LETM1 in cells. Furthermore, the purified LETM1 exhibits Ca2+/H+ anti-transport activity and the activity is enhanced as the proton gradient is increased. More importantly, electron microscopy studies reveal a hexameric LETM1 with a central cavity and also, observe two different conformational states under alkaline and acidic conditions, respectively. Our results indicate that LETM1 is a Ca2+/H+ antiporter and most likely responsible for mitochondrial Ca2+ output.
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