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Abstract：
Eukaryotic NMEs/NDP kinases are a family of 10 multifunctional proteins that occur in different cellular compartments and interact with various cellular components (proteins, membranes, and DNA). In contrast to the well-studied Group I NMEs (NME1-4), little is known about the more divergent Group II NMEs (NME5-9). Three recent publications now shed new light on NME6. First, NME6 is a third mitochondrial NME, largely localized in the matrix space, associated with the mitochondrial inner membrane. Second, while its monomeric form is inactive, NME6 gains NDP kinase activity through interaction with mitochondrial RCC1L. This challenges the current notion that mammalian NMEs require the formation of hexamers to become active. The formation of complexes between NME6 and RCC1L, likely heterodimers, seemingly obviates the necessity for hexamer formation, stabilizing a NDP kinase-competent conformation. Third, NME6 is involved in mitochondrial gene maintenance and expression by providing (d)NTPs for replication and transcription (in particular the pyrimidine nucleotides) and by a less characterized mechanism that supports mitoribosome function. This review offers an overview of NME evolution and structure and highlights the new insight into NME6. The new findings position NME6 as the most comprehensively studied protein in NME Group II and may even suggest it as a new paradigm for related family members.
摘要：
真核NME/NDP激酶是10个多功能蛋白家族，它们存在于不同的细胞区室中，并与各种细胞成分（蛋白质，膜，和DNA）。与经过充分研究的第一组NME(NME1-4)相反，对更不同的第二组NME(NME5-9)知之甚少。最近的三份出版物现在为NME6提供了新的思路。首先,NME6是第三个线粒体NME，大部分位于矩阵空间中，与线粒体内膜有关。第二,虽然它的单体形式是无活性的，NME6通过与线粒体RCC1L相互作用获得NDP激酶活性。这挑战了目前的观点，即哺乳动物NME需要形成六聚体才能变得活跃。NME6与RCC1L的配合物的形成，可能是异二聚体，似乎消除了六聚体形成的必要性，稳定NDP激酶活性构象。第三，NME6通过提供(d)用于复制和转录的NTP(特别是嘧啶核苷酸)和通过支持丝裂体功能的较少表征的机制而参与线粒体基因维持和表达。这篇综述概述了NME的演变和结构，并强调了对NME6的新见解。新发现将NME6定位为NMEII组研究最全面的蛋白质，甚至可能暗示它是相关家族成员的新范例。
