FEBS Letters

Rothman, James E.

doi: 10.1002/1873-3468.13308pmid: 30552677

Puglisi, Rita; Pastore, Annalisa

doi: 10.1002/1873-3468.13245pmid: 30194723

Iron–sulfur cluster biogenesis is a complex process mediated by numerous proteins among which two from bacteria chaperones, called HscB and HscA in bacteria. They are highly conserved up to eukaryotes and homologous to DnaJ and DnaK, respectively, but with specific differences. As compared with other chaperones, HscB and HscA have escaped attention and relatively little is known about their functions. After briefly introducing the various chaperone families, we reviewed here the current structural and functional knowledge HscA and HscB and on their role in cluster formation. We critically evaluated the literature and highlighted the weak aspects which will require more attention in the future. We sincerely hope that this study will inspire new interest on this important and interesting system.

Nakazawa, Masami; Ando, Hiroko; Nishimoto, Ayusa; Ohta, Tsuyoshi; Sakamoto, Kimitoshi; Ishikawa, Takahiro; Ueda, Mitsuhiro; Sakamoto, Tatsuji; Nakano, Yoshihisa; Miyatake, Kazutaka; Inui, Hiroshi

doi: 10.1002/1873-3468.13276pmid: 30328102

In Euglena gracilis, wax ester fermentation produces ATP during anaerobiosis. Here, we report that anaerobic wax ester production is suppressed when the mitochondrial electron transport chain complex I is inhibited by rotenone, whereas it is increased by the uncoupler carbonyl cyanide m‐chlorophenylhydrazone (CCCP). The ADP/ATP ratio in anaerobic cells is elevated by treatment with either rotenone or CCCP. Gene silencing experiments indicate that acyl‐CoA dehydrogenase, electron transfer flavoprotein (ETF), and rhodoquinone (RQ) participate in wax ester production. These results suggest that fatty acids are synthesized in mitochondria by the reversal of β‐oxidation, where trans‐2‐enoyl‐CoA is reduced mainly by acyl‐CoA dehydrogenase using the electrons provided by NADH via the electron transport chain complex I, RQ, and ETF, and that ATP production is highly supported by anaerobic respiration utilizing trans‐2‐enoyl‐CoA as a terminal electron acceptor.

Salvi, Francesca; Trebacz, Malgorzata; Kokot, Thomas; Hoermann, Bernhard; Rios, Pablo; Barabas, Orsolya; Kӧhn, Maja

doi: 10.1002/1873-3468.13284pmid: 30403291

Protein phosphatase‐1 (PP1) drives a large amount of phosphoSer/Thr protein dephosphorylations in eukaryotes to counteract multiple kinases in signaling pathways. The phosphatase requires divalent metal cations for catalytic activity and contains iron naturally. Iron has been suggested to have an influence on PP1 activity through Fe2+ and Fe3+ oxidation states. However, much biochemical and all structural data have been obtained with recombinant PP1 containing Mn2+ ions. Purifying iron‐containing PP1 from Escherichia coli has thus far not been possible. Here, we present the preparation, characterization, and structure of iron‐bound PP1α in inactive and active states. We establish a key role for the electronic/redox properties of iron in PP1 activity and shed light on the difference in substrate specificity between iron‐ and manganese‐containing PP1.

Chi, Xiaodong; Chang, Yunqing; Li, Mengmiao; Lin, Jin; Liu, Yi; Li, Chuanyou; Tang, Shenjie; Zhang, Junjie

doi: 10.1002/1873-3468.13280pmid: 30372528

Toxin‐antitoxin (TA) systems are regarded as genetic modules that facilitate bacterial survival under stress conditions. In this study, a novel TA system in Mycobacterium tuberculosis H37Rv chromosome was identified, termed as mt‐PemIK, which consists of antitoxin mt‐PemI and toxin mt‐PemK (Rv3098A). Induction of mt‐PemK leads to growth arrest in Mycobacterium smegmatis, while the toxic effect of mt‐PemK is eliminated by co‐expression of mt‐PemI. mt‐PemK is characterized as an endoribonuclease whose activity is pH‐dependent. mt‐PemK, as well as some other M. tuberculosis toxin/antitoxin proteins, can be modified by pupylation, suggesting that the Pup‐proteasome system is involved in the regulation of TA systems. These results are helpful to understand the mechanisms of M. tuberculosis growth regulation under stress conditions.

Han, Yawei; Zhang, Kun; Hong, Yuheng; Wang, Jingzhao; Liu, Qi; Zhang, Zhen; Xia, Han; Tang, Yutao; Li, Tengshuai; Li, Liandong; Xue, Yuan; Hong, Wei

doi: 10.1002/1873-3468.13282pmid: 30381822

Fukui, Kenji; Harada, Akiko; Wakamatsu, Taisuke; Minobe, Ai; Ohshita, Koki; Ashiuchi, Makoto; Yano, Takato

doi: 10.1002/1873-3468.13279pmid: 30372520

In plant organelle genomes, homeologous recombination between heteroallelic positions of repetitive sequences is increased by dysfunction of the gene encoding MutS homolog 1 (MSH1), a plant organelle‐specific homolog of bacterial mismatch‐binding protein MutS1. The C‐terminal region of plant MSH1 contains the GIY‐YIG endonuclease motif. The biochemical characteristics of plant MSH1 have not been investigated; accordingly, the molecular mechanism by which plant MSH1 suppresses homeologous recombination is unknown. Here, we characterized the recombinant GIY‐YIG domain of Arabidopsis thaliana MSH1, showing that the domain possesses branched DNA‐specific DNA‐binding activity. Interestingly, the domain exhibited no endonuclease activity, suggesting that the mismatch‐binding domain is required for DNA incision. Based on these results, we propose a possible mechanism for MSH1‐dependent suppression of homeologous recombination.

Zare, Aman; Johansson, Anna‐Mia; Karlsson, Edvin; Delhomme, Nicolas; Stenberg, Per

doi: 10.1002/1873-3468.13278pmid: 30372516

Environmental perturbations induce transcriptional changes, some of which may be inherited even in the absence of the initial stimulus. Previous studies have focused on transfers through the germline although microbiota is also passed on to the offspring. Thus, we inspected the involvement of the gut microbiome in transgenerational inheritance of environmental exposures in Drosophila melanogaster. We grew flies in the cold versus control temperatures and compared their transcriptional patterns in both conditions as well as in their offspring. F2 flies grew in control temperature, while we controlled their microbiota acquisition from either F1 sets. Transcriptional status of some genes was conserved transgenerationally, and a subset of these genes, mainly expressed in the gut, was transcriptionally dependent on the acquired microbiome.

Wu, Wei; Zhou, Hui; He, Fei; Xiao, Zhi; Jiang, Yong; Zhao, Ming

doi: 10.1002/1873-3468.13272pmid: 30317550

G2/M checkpoints ensure the proper timing of cell mitosis. We previously reported that p38 mitogen‐activated protein kinase (MAPK) activation is essential for stress‐induced G2 arrest in the U‐2OS osteosarcoma cell line, but the molecular mechanism was obscure. Here, using the T7 phage display system, we find p38 directly binds to human polycomb protein 2 (HPC2), and arsenate‐induced G2 arrest in U‐2OS cell is p38‐ and phosphorylation of HPC2‐dependent. Phosphorylation of HPC2 at threonine 495 is required for recruiting Ring1 and Rb family proteins to form the polycomb repressive complex (PRC), and PRC is required for arsenate‐induced downregulation of CDC2 expression. Thus, p38 MAPK regulates cell cycle progression through phosphorylation of HPC2 to mediate transcriptional repression, providing a mechanistic link for arsenate‐induced transcriptional silencing.

Wang, Chengliang; Zhan, Li; Wu, Minhao; Ma, Rongsheng; Yao, Jun; Xiong, Ying; Pan, Yang; Guan, Shenheng; Zhang, Xuan; Zang, Jianye

doi: 10.1002/1873-3468.13281pmid: 30381828

Using methods combining cross‐linking, pull‐down assays, and stable isotope labeling by amino acids in cell culture with mass spectrometry, we identified that the Tudor domain‐containing protein Spindlin‐1 recognizes trimethylation of histone H4 lysine 20 (H4K20me3). The binding affinity of Spindlin‐1 to H4K20me3 is weaker than that to H3K4me3, indicating H4K20me3 as a secondary substrate for Spindlin‐1. Structural studies of Spindlin‐1 in complex with the H4K20me3 peptide indicate that Spindlin‐1 attains a distinct binding mode for H4K20me3 recognition. Further biochemical analysis identified that Spindlin‐1 also binds methylated R23 of H4, providing new clues for the function of Spindlin‐1.