Homodimeric intrinsic membrane proteins. Identification and modulation of interactions between mitochondrial transporter (carrier) subunits.
Homodimeric intrinsic membrane proteins. Identification and modulation of interactions between mitochondrial transporter (carrier) subunits.
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同二聚内膜蛋白。
DOI：
10.1016/j.bbrc.2010.02.074
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发表时间：
2010
影响因子：
3.1
通讯作者：
Wohlrab,Hartmut
中科院分区：
文献类型：
--
作者：
Wohlrab,Hartmut
线粒体内膜的转运蛋白（载体）将基质和细胞溶质内的代谢途径与代谢物和无机离子的转运/交换联系起来。氧化磷酸化需要严格控制这些通量。了解大多数转运蛋白发挥作用的三元复杂转运机制需要计算其亚基的数量和相互作用。磷酸盐转运蛋白（PTP，Mir 1 p）亚基很容易形成同源二聚体，亚基间的亲和力可通过突变改变。Cys 28可能位于亚基界面，是产生转运抑制或通道样转运模式的突变位点。这种突变导致亚基之间亲和力的小幅增加或减少。PTP抑制剂N-乙基马来酰亚胺少量降低亚基亲和力。产生最高（40%）和最低（2%）脂质体掺入效率（LIE）的PTP突变聚集在Cys 28附近。这样的突变体亚基分别显示最低和最高的亚基亲和力。草酰乙酸转运蛋白（Oac 1 p）亚基的亲和力几乎是PTP亚基的两倍。Oac 1 p、二羧酸（Dic 1 p）和PTP转运蛋白亚基形成亲和力更低的异源二聚体。这些结果为详细研究奠定了坚实的基础，以确定亚基亲和力对运输模式和活性的影响，并确定防止异二聚体形成的机制，异二聚体肯定会对氧化磷酸化和ATP水平产生负面影响，对细胞产生严重后果。
Transporter (carrier) proteins of the inner mitochondrial membrane link metabolic pathways within the matrix and the cytosol with transport/exchange of metabolites and inorganic ions. Their strict control of these fluxes is required for oxidative phosphorylation. Understanding the ternary complex transport mechanism with which most of these transporters function requires an accounting of the number and interactions of their subunits. The phosphate transporter (PTP, Mir1p) subunit readily forms homodimers with intersubunit affinities changeable by mutations. Cys28, likely at the subunit interface, is a site for mutations yielding transport inhibition or a channel-like transport mode. Such mutations yield a small increase or decrease in affinity between the subunits. The PTP inhibitor N-ethylmaleimide decreases subunit affinity by a small amount. PTP mutations that yield the highest (40%) and the lowest (2%) liposome incorporation efficiencies (LIE) are clustered near Cys28. Such mutant subunits show the lowest and highest subunit affinities respectively. The oxaloacetate transporter (Oac1p) subunit has an almost twofold lower affinity than the PTP subunit. The Oac1p, dicarboxylate (Dic1p) and PTP transporter subunits form heterodimers with even lower affinities. These results form a firm basis for detailed studies to establish the effect of subunit affinities on transport mode and activity and for the identification of the mechanism that prevents formation of heterodimers that surely will negatively impact oxidative phosphorylation and ATP levels with serious consequences for the cell.
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影响因子：
5.6
作者：
Lee, Seok-Yong;Letts, James A.;MacKinnon, Roderick
通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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