Characterization and Cloning of a Nucleoside-diphosphate Kinase Targeted to Matrix of Mitochondria in Pigeon

Lambeth, David O.; Mehus, James G.; Ivey, Mary A.; Milavetz, Barry

doi:10.1074/jbc.272.39.24604

Cited by 41 publications

(44 citation statements)

References 51 publications

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“…In Drosophila NDP kinase, in which proline is present in the wild-type, the natural K-pn mutation destabilizes the hexamer (17), and in Dictyostelium, site-directed mutagenesis achieves the same result (18). An exception may be the NDP kinase purified from the matrix of pigeon mitochondria, which appears to be highly stable despite the presence of a serine at this position (19).…”

Section: Discussionmentioning

confidence: 99%

“…Characteristics of the N-terminal extension prompted the authors to propose localization to the intermembrane space of mitochondria (29). A mitochondrial NDP kinase was reported in pigeon liver, specifically associated to the matrix (19). We have reported the identification of nm23-H4 cDNA encoding a protein homologous to NDP kinases that presents characteristics suggesting targeting to mitochondria (6).…”

Section: /Ebi Data Bank With Accession Number(s) Y07604 (Nm23-h4 Cdnamentioning

confidence: 99%

“…Among the mitochondrial NDP kinases purified to date, Nm23-H4 is the first to be shown to be clearly associated with the mitochondrial membranes. The pigeon NDP kinase purified from the matrix fraction was found to be soluble in the supernatant of sonicated mitochondria (19). A pea mitochondrial NDP kinase, which has been partially sequenced, was purified from a soluble fraction proposed to be the intermembrane space based on difference in accessibility of the ATP substrate (56).…”

Section: Discussionmentioning

confidence: 99%

“…The K-pn mutation substitutes a serine for a proline in a surface loop, named for this reason the K-pn loop, that makes subunit contacts in the hexamer and plays an important part in the stability of the hexamers (17,18). The proline residue is conserved in most NDP kinases, but it is a serine in Nm23-H4 (6) and in the NDP kinase of pigeon liver mitochondria (19).…”

Section: /Ebi Data Bank With Accession Number(s) Y07604 (Nm23-h4 Cdnamentioning

confidence: 99%

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The Human nm23-H4 Gene Product Is a Mitochondrial Nucleoside Diphosphate Kinase

Milon¹,

Meyer²,

Chiadmi³

et al. 2000

Journal of Biological Chemistry

134

129

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We demonstrate here the catalytic activity and subcellular localization of the Nm23-H4 protein, product of nm23-H4, a new member of the human nm23/nucleoside diphosphate (NDP) kinase gene family (Milon, L., Rousseau-Merck, M., Munier, A., Erent, M., Lascu, I., Capeau, J., and Lacombe, M. L. (1997) Hum. Genet. 99, 550 -557). Nm3-H4 was synthesized in escherichia coli as the fulllength protein and as a truncated form missing the Nterminal extension characteristic of mitochondrial targeting. The truncated form possesses NDP kinase activity, whereas the full-length protein is inactive, suggesting that the extension prevents enzyme folding and/or activity. X-ray crystallographic analysis was performed on active truncated Nm23-H4. Like other eukaryotic NDP kinases, it is a hexamer. Nm23-H4 naturally possesses a serine residue at position 129, equivalent to the K-pn mutation of the Drosophila NDP kinase. The x-ray structure shows that the presence of Ser 129 has local structural effects that weaken subunit interactions. Site-directed mutagenesis shows that the serine is responsible for the lability of Nm23-H4 to heat and urea treatment, because the S129P mutant is greatly stabilized. Examination of human embryonic kidney 293 cells transfected with green fluorescent protein fusions by confocal microscopy shows a specific mitochondrial localization of Nm23-H4 that was also demonstrated by Western blot analysis of subcellular fractions of these cells. Import into mitochondria is accompanied by cleavage of the N-terminal extension that results in NDP kinase activity. Submitochondrial fractionation indicates that Nm23-H4 is associated with mitochondrial membranes, possibly to the contact sites between the outer and inner membranes.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: /Ebi Data Bank With Accession Number(s) Y07604 (Nm23-h4 Cdnamentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: /Ebi Data Bank With Accession Number(s) Y07604 (Nm23-h4 Cdnamentioning

confidence: 99%

See 2 more Smart Citations

The Human nm23-H4 Gene Product Is a Mitochondrial Nucleoside Diphosphate Kinase

Milon¹,

Meyer²,

Chiadmi³

et al. 2000

Journal of Biological Chemistry

134

129

View full text Add to dashboard Cite

show abstract

“…NDPK isoforms have been found in the matrix as well as in the inter-membrane space of mitochondria (Troll et al, 1993;Lambeth et al, 1997;Milon et al, 1997;Struglics and Håkansson, 1999). In animals, matrix NDPK isoforms have been suggested to catalyze transfer of the phosphoryl group from GTP, produced by the TCA cycle, to ATP (Herbert et al, 1955).…”

mentioning

confidence: 99%

Heat Stress Response in Pea Involves Interaction of Mitochondrial Nucleoside Diphosphate Kinase with a Novel 86-Kilodalton Protein

et al. 2001

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In this work we have further characterized the first mitochondrial nucleoside diphosphate kinase (mtNDPK) isolated from plants. The mitochondrial isoform was found to be especially abundant in reproductive and young tissues. Expression of the pea (Pisum sativum L. cv Oregon sugarpod) mtNDPK was not affected by different stress conditions. However, the pea mtNDPK was found to interact with a novel 86-kD protein, which is de novo synthesized in pea leaves upon exposure to heat. Thus, we have evidence for the involvement of mtNDPK in mitochondrial heat response in pea in vivo. Studies on oligomerization revealed that mtNDPK was found in complexes of various sizes, corresponding to the sizes of e.g. hexamers, tetramers, and dimers, indicating flexibility in oligomerization. This flexibility, also found for other NDPK isoforms, has been correlated with the ability of this enzyme to interact with other proteins. We believe that the mtNDPK is involved in heat stress response in pea, possibly as a modulator of the 86-kD protein.

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A novel human nucleoside diphosphate (NDP) kinase, Nm23-H6, localizes in mitochondria and affects cytokinesis

et al. 2000

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Nucleoside diphosphate kinases (NDP kinases) are enzymes known to be conserved throughout evolution and have been shown to be involved in various biological events, in addition to the "housekeeping" phosphotransferase activity. We present the molecular cloning of a novel human NDP kinase gene, termed Nm23-H6. Nm23-H6 gene has been mapped at chromosome 3p21.3 and is highly expressed in heart, placenta, skeletal muscle, and some of the cancer cell lines. Recombinant Nm23-H6 protein has been identified to exhibit functional NDP kinase activity. Immunolocalization studies showed that both endogenous and inducibly expressed Nm23-H6 proteins were present as short, filament-like, perinuclear radical arrays and that they colocalized with mitochondria. Cell fractionation study also demonstrated the presence of Nm23-H6 protein in a mitochondria-rich fraction. Moreover, induction of overexpression of Nm23-H6 in SAOS2 cells, using the Cre-loxP gene activation system, resulted in growth suppression and generation of multinucleated cells. Flow cytometric analysis also demonstrated that the proportion of cells with more than 4N DNA content increased to 28.1% after induction of Nm23-H6, coinciding with the appearance of multinucleated cells. These observations suggest that Nm23-H6, a new member of the NDP kinase family, resides in mitochondria and plays a role in regulation of cell growth and cell cycle progression.

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Characterization and Cloning of a Nucleoside-diphosphate Kinase Targeted to Matrix of Mitochondria in Pigeon

Cited by 41 publications

References 51 publications

The Human nm23-H4 Gene Product Is a Mitochondrial Nucleoside Diphosphate Kinase

The Human nm23-H4 Gene Product Is a Mitochondrial Nucleoside Diphosphate Kinase

Heat Stress Response in Pea Involves Interaction of Mitochondrial Nucleoside Diphosphate Kinase with a Novel 86-Kilodalton Protein

A novel human nucleoside diphosphate (NDP) kinase, Nm23-H6, localizes in mitochondria and affects cytokinesis

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