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Dive into the research topics where Rachel Nechushtai is active.

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Featured researches published by Rachel Nechushtai.


Biochimica et Biophysica Acta | 1999

The biogenesis and assembly of photosynthetic proteins in thylakoid membranes

Francis-André Wollman; Limor Minai; Rachel Nechushtai

3. Conveyance of the PPs to the thylakoid membranes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 3.1. Site of translation of the cyanobacterial and chloroplast-encoded PP subunits . . . . . . . 30 3.2. Targeting to the organelle and import . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 3.3. Maturation of the precursor: the processing step . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 3.4. Insertion, assembly and translocation into the thylakoid membranes . . . . . . . . . . . . . . 34


Proceedings of the National Academy of Sciences of the United States of America | 2007

MitoNEET is a uniquely folded 2Fe 2S outer mitochondrial membrane protein stabilized by pioglitazone.

Mark L. Paddock; Sandra E. Wiley; Herbert L. Axelrod; Aina E. Cohen; Melinda Roy; Edward C. Abresch; Dominique T. Capraro; Anne N. Murphy; Rachel Nechushtai; Jack E. Dixon; Patricia A. Jennings

Iron–sulfur (Fe–S) proteins are key players in vital processes involving energy homeostasis and metabolism from the simplest to most complex organisms. We report a 1.5 Å x-ray crystal structure of the first identified outer mitochondrial membrane Fe–S protein, mitoNEET. Two protomers intertwine to form a unique dimeric structure that constitutes a new fold to not only the ≈650 reported Fe–S protein structures but also to all known proteins. We name this motif the NEET fold. The protomers form a two-domain structure: a β-cap domain and a cluster-binding domain that coordinates two acid-labile 2Fe–2S clusters. Binding of pioglitazone, an insulin-sensitizing thiazolidinedione used in the treatment of type 2 diabetes, stabilizes the protein against 2Fe–2S cluster release. The biophysical properties of mitoNEET suggest that it may participate in a redox-sensitive signaling and/or in Fe–S cluster transfer.


Nature Communications | 2012

Integrated photosystem II-based photo-bioelectrochemical cells

Omer Yehezkeli; Ran Tel-Vered; Julian Wasserman; Alexander Trifonov; Dorit Michaeli; Rachel Nechushtai; Itamar Willner

Photosynthesis is a sustainable process that converts light energy into chemical energy. Substantial research efforts are directed towards the application of the photosynthetic reaction centres, photosystems I and II, as active components for the light-induced generation of electrical power or fuel products. Nonetheless, no integrated photo-bioelectrochemical device that produces electrical power, upon irradiation of an aqueous solution that includes two inter-connected electrodes is known. Here we report the assembly of photobiofuel cells that generate electricity upon irradiation of biomaterial-functionalized electrodes in aqueous solutions. The cells are composed of electrically contacted photosystem II-functionalized photoanodes and an electrically wired bilirubin oxidase/carbon nanotubes-modified cathode. Illumination of the photoanodes yields the oxidation of water to O(2) and the transfer of electrons through the external circuit to the cathode, where O(2) is re-reduced to water.


Journal of Biological Chemistry | 2007

The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster

Sandra E. Wiley; Mark L. Paddock; Edward C. Abresch; Larry A. Gross; Peter van der Geer; Rachel Nechushtai; Anne N. Murphy; Patricia A. Jennings; Jack E. Dixon

The outer mitochondrial membrane protein mitoNEET was discovered as a binding target of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class used to treat type 2 diabetes (Colca, J. R., McDonald, W. G., Waldon, D. J., Leone, J. W., Lull, J. M., Bannow, C. A., Lund, E. T., and Mathews, W. R. (2004) Am. J. Physiol. 286, E252–E260). We have shown that mitoNEET is a member of a small family of proteins containing a 39-amino-acid CDGSH domain. Although the CDGSH domain is annotated as a zinc finger motif, mitoNEET was shown to contain iron (Wiley, S. E., Murphy, A. N., Ross, S. A., van der Geer, P., and Dixon, J. E. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 5318–5323). Optical and electron paramagnetic resonance spectroscopy showed that it contained a redox-active pH-labile Fe-S cluster. Mass spectrometry showed the loss of 2Fe and 2S upon cofactor extrusion. Spectroscopic studies of recombinant proteins showed that the 2Fe-2S cluster was coordinated by Cys-3 and His-1. The His ligand was shown to be involved in the observed pH lability of the cluster, indicating that loss of this ligand via protonation triggered release of the cluster. mitoNEET is the first identified 2Fe-2S-containing protein located in the outer mitochondrial membrane. Based on the biophysical data and domain fusion analysis, mitoNEET may function in Fe-S cluster shuttling and/or in redox reactions.


Photosynthesis Research | 1995

Function and organization of Photosystem I polypeptides.

Parag R. Chitnis; Qiang Xu; Vaishali P. Chitnis; Rachel Nechushtai

Photosystem I functions as a plastocyanin:ferredoxin oxidoreductase in the thylakoid membranes of chloroplasts and cyanobacteria. The PS I complex contains the photosynthetic pigments, the reaction center P700, and five electron transfer centers (A0, A1, FX, FA, and FB) that are bound to the PsaA, PsaB, and PsaC proteins. In addition, PS I complex contains at least eight other polypeptides that are accessory in their functions. Recent use of cyanobacterial molecular genetics has revealed functions of the accessory subunits of PS I. Site-directed mutagenesis is now being used to explore structure-function relations in PS I. The overall architecture of PSI complex has been revealed by X-ray crystallography, electron microscopy, and biochemical methods. The information obtained by different techniques can be used to propose a model for the organization of PS I. Spectroscopic and molecular genetic techniques have deciphered interaction of PS I proteins with the soluble electron transfer partners. This review focuses on the recent structural, biochemical and molecular genetic studies that decipher topology and functions of PS I proteins, and their interactions with soluble electron carriers.


FEBS Letters | 1988

Nucleotide sequence of cDNA clones encoding the entire precursor polypeptides for subunits IV and V of the photosystem I reaction center from spinach

Johannes Steppuhn; J. Hermans; Rachel Nechushtai; Ulf Ljungberg; Fritz Thümmler; F. Lottspeich; Reinhold G. Herrmann

Using λgt11 expression cloning and immunoscreening, cDNA‐containing recombinant phages for subunits IV and V of the photosystem I reaction center were isolated, sequenced and used to probe Northern blots of polyadenylated RNA prepared from spinach seedlings. The mRNA sizes for both components are ∼ 1000 and 850 nucleotides, respectively. The 968 nucleotide cDNA sequence and derived amino acid sequence for subunit IV predict a single open reading frame of 231 amino acid residues (25.4 kDa). Comparison with a 13‐residue N‐terminal amino acid sequence determined for subunit IV suggests a mature protein of 17.3 kDa (154 residues) and a transit sequence of 77 amino acids (8.1 kDa). The corresponding data for subunit V are 677 bp (cDNA), 167 residues for the precursor protein (18.2 kDa), 98 residues for the mature polypeptide (10.8 kDa) and 69 residues for the transit peptide (7.4 kDa). Secondary structure predictions indicate that both proteins possess greatly different transit sequences and that none is membrane‐spanning.


Proceedings of the National Academy of Sciences of the United States of America | 2011

Facile transfer of [2Fe-2S] clusters from the diabetes drug target mitoNEET to an apo-acceptor protein

John A. Zuris; Yael Harir; Andrea R. Conlan; Maya Shvartsman; Dorit Michaeli; Sagi Tamir; Mark L. Paddock; José N. Onuchic; Ron Mittler; Zvi Ioav Cabantchik; Patricia A. Jennings; Rachel Nechushtai

MitoNEET (mNT) is an outer mitochondrial membrane target of the thiazolidinedione diabetes drugs with a unique fold and a labile [2Fe-2S] cluster. The rare 1-His and 3-Cys coordination of mNT’s [2Fe-2S] leads to cluster lability that is strongly dependent on the presence of the single histidine ligand (His87). These properties of mNT are similar to known [2Fe-2S] shuttle proteins. Here we investigated whether mNT is capable of cluster transfer to acceptor protein(s). Facile [2Fe-2S] cluster transfer is observed between oxidized mNT and apo-ferredoxin (a-Fd) using UV-VIS spectroscopy and native-PAGE, as well as with a mitochondrial iron detection assay in cells. The transfer is unidirectional, proceeds to completion, and occurs with a second-order-reaction rate that is comparable to known iron-sulfur transfer proteins. Mutagenesis of His87 with Cys (H87C) inhibits transfer of the [2Fe-2S] clusters to a-Fd. This inhibition is beyond that expected from increased cluster kinetic stability, as the equivalently stable Lys55 to Glu (K55E) mutation did not inhibit transfer. The H87C mutant also failed to transfer its iron to mitochondria in HEK293 cells. The diabetes drug pioglitazone inhibits iron transfer from WT mNT to mitochondria, indicating that pioglitazone affects a specific property, [2Fe-2S] cluster transfer, in the cellular environment. This finding is interesting in light of the role of iron overload in diabetes. Our findings suggest a likely role for mNT in [2Fe-2S] and/or iron transfer to acceptor proteins and support the idea that pioglitazone’s antidiabetic mode of action may, in part, be to inhibit transfer of mNT’s [2Fe-2S] cluster.


Journal of Molecular Biology | 2009

Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2.

Andrea R. Conlan; Herbert L. Axelrod; Aina E. Cohen; Edward C. Abresch; John A. Zuris; David Yee; Rachel Nechushtai; Patricia A. Jennings; Mark L. Paddock

The endoplasmic reticulum protein Miner1 is essential for health and longevity. Mis-splicing of CISD2, which codes for Miner1, is causative in Wolfram Syndrome 2 (WFS2) resulting in early onset optic atrophy, diabetes mellitus, deafness and decreased lifespan. In knock-out studies, disruption of CISD2 leads to accelerated aging, blindness and muscle atrophy. In this work, we characterized the soluble region of human Miner1 and solved its crystal structure to a resolution of 2.1 A (R-factor=17%). Although originally annotated as a zinc finger, we show that Miner1 is a homodimer harboring two redox-active 2Fe-2S clusters, indicating for the first time an association of a redox-active FeS protein with WFS2. Each 2Fe-2S cluster is bound by a rare Cys(3)-His motif within a 17 amino acid segment. Miner1 is the first functionally different protein that shares the NEET fold with its recently identified paralog mitoNEET, an outer mitochondrial membrane protein. We report the first measurement of the redox potentials (E(m)) of Miner1 and mitoNEET, showing that they are proton-coupled with E(m) approximately 0 mV at pH 7.5. Changes in the pH sensitivity of their cluster stabilities are attributed to significant differences in the electrostatic distribution and surfaces between the two proteins. The structural and biophysical results are discussed in relation to possible roles of Miner1 in cellular Fe-S management and redox reactions.


Proceedings of the National Academy of Sciences of the United States of America | 2013

NAF-1 and mitoNEET are central to human breast cancer proliferation by maintaining mitochondrial homeostasis and promoting tumor growth

Yang-Sung Sohn; Sagi Tamir; Luhua Song; Dorit Michaeli; Imad Matouk; Andrea R. Conlan; Yael Harir; Sarah H. Holt; Vladimir Shulaev; Mark L. Paddock; Abraham Hochberg; Ioav Z. Cabanchick; José N. Onuchic; Patricia A. Jennings; Rachel Nechushtai; Ron Mittler

Mitochondria are emerging as important players in the transformation process of cells, maintaining the biosynthetic and energetic capacities of cancer cells and serving as one of the primary sites of apoptosis and autophagy regulation. Although several avenues of cancer therapy have focused on mitochondria, progress in developing mitochondria-targeting anticancer drugs nonetheless has been slow, owing to the limited number of known mitochondrial target proteins that link metabolism with autophagy or cell death. Recent studies have demonstrated that two members of the newly discovered family of NEET proteins, NAF-1 (CISD2) and mitoNEET (mNT; CISD1), could play such a role in cancer cells. NAF-1 was shown to be a key player in regulating autophagy, and mNT was proposed to mediate iron and reactive oxygen homeostasis in mitochondria. Here we show that the protein levels of NAF-1 and mNT are elevated in human epithelial breast cancer cells, and that suppressing the level of these proteins using shRNA results in significantly reduced cell proliferation and tumor growth, decreased mitochondrial performance, uncontrolled accumulation of iron and reactive oxygen in mitochondria, and activation of autophagy. Our findings highlight NEET proteins as promising mitochondrial targets for cancer therapy.


Photosynthesis Research | 2014

Photosynthetic reaction center-functionalized electrodes for photo-bioelectrochemical cells

Omer Yehezkeli; Ran Tel-Vered; Dorit Michaeli; Itamar Willner; Rachel Nechushtai

During the last few years, intensive research efforts have been directed toward the application of several highly efficient light-harvesting photosynthetic proteins, including reaction centers (RCs), photosystem I (PSI), and photosystem II (PSII), as key components in the light-triggered generation of fuels or electrical power. This review highlights recent advances for the nano-engineering of photo-bioelectrochemical cells through the assembly of the photosynthetic proteins on electrode surfaces. Various strategies to immobilize the photosynthetic complexes on conductive surfaces and different methodologies to electrically wire them with the electrode supports are presented. The different photoelectrochemical systems exhibit a wide range of photocurrent intensities and power outputs that sharply depend on the nano-engineering strategy and the electroactive components. Such cells are promising candidates for a future production of biologically-driven solar power.

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Itamar Willner

Hebrew University of Jerusalem

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Ron Mittler

University of North Texas

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Dorit Michaeli

Hebrew University of Jerusalem

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Yang Sung Sohn

Hebrew University of Jerusalem

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John A. Zuris

University of California

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Sagi Tamir

Hebrew University of Jerusalem

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