Article
Biochemistry & Molecular Biology
Feifei Sun, Xinpei Wang, Jing Hu, Junmei Liu, Xin Wang, Wenqiao Jia, Zeyuan Yu, Lin Gao, Baokai Dou, Ru Zhao, Tingting Feng, Xueli Wang, Wenbo Zhang, Hui Liu, Kaihua Liu, Yang Shao, Xuesen Dong, Bo Han
Summary: This study reveals that RUVBL1 is upregulated in ENZR cells and prostate tumors, and its expression is increased by enzalutamide. RUVBL1 promotes ENZR progression through the activation of the MAPK pathway. Co-overexpression of RUVBL1 and PLXNA1 is associated with a poor prognosis in prostate cancer patients.
Article
Multidisciplinary Sciences
Anthony D. Rish, Zhangfei Shen, Zhenhang Chen, Nan Zhang, Qingfei Zheng, Tian-Min Fu
Summary: This study reports two cryo-EM structures of RuvB, revealing the mechanism of HJ branch migration. RuvB assembles into a spiral staircase, ring-like hexamer, enveloping double-stranded DNA. The asymmetric assembly of RuvB explains the 6:4 stoichiometry of the RuvB/RuvA complex in coordinating HJ migration in bacteria. These findings provide a mechanistic understanding of HJ branch migration facilitated by RuvB, which may be universally shared by prokaryotic and eukaryotic organisms.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Hisham Mazal, Marija Iljina, Inbal Riven, Gilad Haran
Summary: Recent research on AAA+ ring-shaped machines such as ClpB and Hsp104 has revealed that pore loops undergo large-amplitude fluctuations on the microsecond time scale and change their conformation in an ATP-dependent manner during substrate threading. The conformational dynamics of certain pore loops strongly correlate with disaggregation activity, suggesting they play a key role in substrate pulling. These findings support the proposal of an ultrafast Brownian-ratchet translocation mechanism that likely acts in parallel to the slower hand-over-hand process in AAA+ machines like ClpB.
Review
Chemistry, Medicinal
Gang Zhang, Shan Li, Kai-Wen Cheng, Tsui-Fen Chou
Summary: AAA ATPases, essential enzymes found in all organisms, are involved in various cellular activities. Researchers have identified and developed small-molecule inhibitors against these enzymes. Structural information suggests further development of specific AAA ATPase inhibitors in the future.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Dina Aweida, Shenhav Cohen
Summary: Protein degradation is essential for cellular integrity, with autophagy and the UPS being the main systems responsible for protein breakdown. Recent studies show that even complex protein structures can be efficiently degraded in vivo, with AAA-ATPases playing a crucial role in the disassembly process.
Article
Biochemistry & Molecular Biology
Camilla Henriksen, Kristoffer T. Baek, Katarzyna Wacnik, Clement Gallay, Jan-Willem Veening, Simon J. Foster, Dorte Frees
Summary: This study provides genetic evidence for the role of ClpX unfoldase activity in coordinating bacterial cell division. The study shows that a Staphylococcus aureus clpX mutant with a spontaneously acquired G325V substitution in the essential FtsA protein's ATP-binding domain can rescue the growth defect. The results also suggest that ClpX promotes septum synthesis by antagonizing FtsA interactions.
MOLECULAR MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Gang Zhang, Feng Wang, Shan Li, Kai-Wen Cheng, Yingying Zhu, Ran Huo, Elyar Abdukirim, Guifeng Kang, Tsui-Fen Chou
Summary: RUVBL1 and RUVBL2 are highly conserved AAA ATPases that play a significant role in cancer progression. This study utilized docking-based virtual screening to identify compounds that inhibit the RUVBL1/2 complex. Seven compounds were found to have inhibitory activity in enzymatic and cellular assays. A series of pyrazolo[1,5-a]pyrimidine-3-carboxamide analogs were synthesized based on compound 15, which showed good potential for structural manipulation. Analysis of the structure-activity relationship revealed the importance of the benzyl group on R2 and the aromatic ring-substituted piperazinyl on R4 for inhibitory activity. Compound 18 exhibited the strongest inhibition and showed potential anticancer activity in multiple cell lines. Proteomic analysis identified cellular proteins dysregulated by compounds 16, 18, and 19. These findings suggest that compound 18 could serve as a starting point for structural modifications to improve potential therapeutic molecules.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Biology
Rebecca Brinkschulte, David M. Fusshoeller, Florian Hoss, Juan F. Rodriguez-Alcazar, Mario A. Lauterbach, Carl-Christian Kolbe, Melanie Rauen, Semra Ince, Christian Herrmann, Eicke Latz, Matthias Geyer
Summary: This study investigates the intrinsic ATP hydrolysis activity of the inflammasomal protein NLRP3 and reveals the activity difference in different conformational states. Site-directed mutagenesis of canonical residues in the nucleotide binding site is analyzed and it is found that the NLRP3 hydrolysis activity correlates with inflammasome activity.
COMMUNICATIONS BIOLOGY
(2022)
Article
Plant Sciences
Eva Dvorak Tomastikova, Fen Yang, Kristina Mlynarova, Said Hafidh, Sarka Schorova, Alzbeta Kusova, Marketa Pernisova, Tereza Prerovska, Bozena Klodova, David Honys, Jiri Fajkus, Ales Pecinka, Petra Prochazkova Schrumpfova
Summary: RUVBL1 and RUVBL2 are crucial for the proper development of male and female gametophytes in Arabidopsis. Mutations in these genes result in abnormal embryo sac structure and nuclear numbers. The expression of these proteins is observed in pollen grains, embryo sac, and tapetum cells, playing important roles in reproductive development.
Article
Plant Sciences
Bowei Jia, Hongli Cui, Dajian Zhang, Bingshuang Hu, Yuan Li, Yang Shen, Xiaoxi Cai, Xiaoli Sun, Mingzhe Sun
Summary: This study investigated the soybean plasma membrane H+-ATPase and found its high conservation in terms of gene structure, protein sequence, and biochemical characteristics. The study confirmed the conserved function of soybean PM H+-ATPases in enhancing tolerance to high pH and sodium bicarbonate stresses. The transcriptional expression of these PM H+-ATPases varied in different tissues and under sodium bicarbonate stress.
PLANT PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Biology
Janelle J. Y. Chuah, Tiffany A. Thibaudeau, David M. Smith
Summary: An HbYX-like dipeptide induces gate-opening in archaeal, yeast, and mammalian 20S proteasomes, stimulates proteasome activity, and reverses inhibition of the proteasome by toxic protein oligomers that are implicated in various neurodegenerative diseases. The findings suggest that HbYX-like molecules have robust potential to stimulate proteasome function and may be useful for treating neurodegenerative diseases.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Julianna R. Cresti, Abramo J. Manfredonia, Christopher E. Braganca, Joseph A. Boscia, Christina M. Hurley, Mary D. Cundiff, Daniel A. Kraut
Summary: The 26S proteasome, responsible for protein degradation in eukaryotic cells, transitions between substrate-accepting and substrate-processing conformations, with important intramolecular interactions stabilizing these conformations. A new conformationally sensitive assay revealed that interactions involving Rpn5 and Rpn2 are crucial for stabilizing substrate-processing conformations, impacting the proteasome's ability to successfully unfold and degrade difficult substrates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Xin-Fu Yan, Chunxi Yang, Mingfang Wang, Yonlada Yong, Yinyue Deng, Yong-Gui Gao
Summary: GtrR is a global transcriptional regulator downstream RpfR, recognizing GTP and possessing moderate GTPase activity. Specific residues like K170, D236, R311, and R357 are crucial for its biological function, mutation of any leading to complete abolishment of GtrR activity.
Article
Multidisciplinary Sciences
Arjun Saha, Arieh Warshel
Summary: This study explored the molecular basis of substrate translocation by the AAA+ motor of the 26S proteasome using simulation approaches, revealing the role of electrostatic interactions and validating the involvement of bulkier residues in pore loop 1 in substrate translocation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Yujin Kang, Carol Cho, Kyung Suk Lee, Ji-Joon Song, Ja Yil Lee
Summary: The research reveals that Abo1 is able to load H3-H4 histones onto DNA, but lacks the capability to load H2A-H2B histones. Additionally, Abo1 exhibits weak binding to DNA regardless of the presence of ATP, and neither histone nor DNA can stimulate its ATP hydrolysis activity.
MOLECULES AND CELLS
(2021)
Article
Biochemistry & Molecular Biology
Armelle Vigouroux, Magali Aumont-Nicaise, Alain Boussac, Loic Marty, Lea Lo Bello, Pierre Legrand, Karl Brillet, Isabelle J. Schalk, Solange Morera
Article
Biochemistry & Molecular Biology
Armelle Vigouroux, Jeanne Dore, Loic Marty, Magali Aumont-Nicaise, Pierre Legrand, Yves Dessaux, Ludovic Vial, Solange Morera
BIOCHEMICAL JOURNAL
(2020)
Article
Biochemistry & Molecular Biology
Edwige Belotti, Nicolas Lacoste, Thomas Simonet, Christophe Papin, Kiran Padmanabhan, Isabella Scionti, Yann-Gael Gangloff, Lorrie Ramos, Defne Dalkara, Ali Hamiche, Stefan Dimitrov, Laurent Schaeffer
NUCLEIC ACIDS RESEARCH
(2020)
Review
Oncology
Quentin Fuchs, Marina Pierrevelcin, Melissa Messe, Benoit Lhermitte, Anne-Florence Blandin, Christophe Papin, Andres Coca, Monique Dontenwill, Natacha Entz-Werle
Article
Plant Sciences
Jaroslav Nisler, David Kopecny, Zuzana Pekna, Radka Koncitikova, Radoslav Koprna, Nino Murvanidze, Stefaan P. O. Werbrouck, Libor Havlicek, Nuria De Diego, Martina Kopecna, Zdenek Wimmer, Pierre Briozzo, Solange Morera, David Zalabak, Lukas Spichal, Miroslav Strnad
Summary: Increasing crop productivity through the synthesis of new CKX inhibitors has been shown to positively impact plant growth, stress resistance, and seed yield. Targeting the cytokinin oxidase/dehydrogenase enzyme offers great potential in plant biotechnology and agriculture.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Biochemistry & Molecular Biology
Christophe Papin, Stephanie Le Gras, Abdulkhaleg Ibrahim, Hatem Salem, Mohammad Mahdi Karimi, Isabelle Stoll, Iva Ugrinova, Maria Schroder, Emeline Fontaine-Pelletier, Ziad Omran, Christian Bronner, Stefan Dimitrov, Ali Hamiche
Summary: Epigenetic modifications and nucleosome positioning are important in gene expression regulation. CpG density, promoter activity, and histone marks accumulation are correlated. CGI boundaries define chromatin promoter regions for epigenetic modifications, while H2A.Z presence is not related to transcriptional control.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Saida Mouffok, Regine Capeyrou, Kamila Belhabich-Baumas, Clement Joret, Anthony K. Henras, Odile Humbert, Yves Henry
Summary: Prp43 is a DEAH-box RNA helicase involved in splicing and ribosome biogenesis, stimulated by co-activators with a G-patch domain. Interaction of G-patch proteins Pfa1 and PINX1 with Prp43 differs, but both rely on the protruding loop between beta 4 and beta 5 strands of Prp43. Disruption of this loop affects Prp43 activity in yeast ribosome biogenesis, suggesting its crucial role in conformational changes induced by G-patch binding.
Article
Biochemistry & Molecular Biology
Armelle Vigouroux, Thibault Meyer, Anais Naretto, Pierre Legrand, Magali Aumont-Nicaise, Aurelie Di Cicco, Sebastien Renoud, Jeanne Dore, Daniel Levy, Ludovic Vial, Celine Lavire, Solange Morera
Summary: The species-specific region SpG8-1b plays a critical role in controlling the transition between rhizospheric and pathogenic lifestyles of the plant pathogen. The transcriptional regulator Atu1419, belonging to the VanR group of GntR superfamily, represses genes in the HCAs catabolic pathway and is regulated by the effector molecule N5,N10-methylenetetrahydrofolate. The study sheds light on the allosteric mechanism of transcription employed by this GntR repressor.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Abdulkhaleg Ibrahim, Christophe Papin, Kareem Mohideen-Abdul, Stephanie Le Gras, Isabelle Stoll, Christian Bronner, Stefan Dimitrov, Bruno P. Klaholz, Ali Hamiche
Summary: Studies have shown that MeCP2 is a microsatellite DNA binding protein that specifically recognizes 5hmC-modified CA repeat sequences, maintaining nucleosome-free regions in the genome. Dysfunction of MeCP2 may play a role in Rett syndrome.
Article
Multidisciplinary Sciences
Mariam Jaafar, Julia Contreras, Carine Dominique, Sara Martin-Villanueva, Regine Capeyrou, Patrice Vitali, Olga Rodriguez-Galan, Carmen Velasco, Odile Humbert, Nicholas J. Watkins, Eduardo Villalobo, Katherine E. Bohnsack, Markus T. Bohnsack, Yves Henry, Raghida Abou Merhi, Jesus de la Cruz, Anthony K. Henras
Summary: This study investigates the functions of box C/D snoRNP snR190 and helicase Dbp7 in eukaryotic ribosome biogenesis. The snR190 snoRNA acts as an RNA chaperone to assist in structuring 25S rRNA, while Dbp7 is crucial for facilitating remodeling events in the peptidyl transferase center region of 25S rRNAs. The molecular events underlying the assembly and maturation of early pre-60S particles during eukaryotic ribosome synthesis are complex and not well understood.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Anne Soisig Steunou, Armelle Vigouroux, Magali Aumont-Nicaise, Stephane Plancqueel, Alain Boussac, Soufian Ouchane, Solange Morera
Summary: This study investigates the regulation and role of periplasmic proteins FtrA and FtrB in the FtrABCD iron transporter. Through crystallography and biophysical methods, the metal binding mode and redox state of FtrA are explored, revealing a new functional model for iron utilization. The study provides new insights into the mechanism of iron transport.
Article
Biochemistry & Molecular Biology
Emeline Fontaine, Christophe Papin, Guillaume Martinez, Stephanie Le Gras, Roland Abi Nahed, Patrick Hery, Thierry Buchou, Khalid Ouararhni, Bertrand Favier, Thierry Gautier, Jamal S. M. Sabir, Matthieu Gerard, Jan Bednar, Christophe Arnoult, Stefan Dimitrov, Ali Hamiche
Summary: The histone variant H3.3, encoded by genes H3f3a and H3f3b, plays an important role in spermatogenesis. This study demonstrates that H3.3B is required for spermatogenesis and male fertility, and its absence leads to alterations in meiotic/post-meiotic transition. The depletion of H3.3B in meiotic cells is associated with increased expression of whole sex chromosomes and retrotransposons, while the expression of piRNA clusters is down-regulated.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Ali Khreiss, Regine Capeyrou, Simon Lebaron, Benjamin Albert, Katherine E. Bohnsack, Markus T. Bohnsack, Yves Henry, Anthony K. Henras, Odile Humbert
Summary: Ribosomes are ribozymes that require proper folding of rRNAs for catalytic activity. Dbp6, an RNA helicase, plays a role in rRNA folding during ribosome biogenesis. Dbp6 exhibits ATPase, annealing, and clamping activities, which are regulated by ATP, and it interacts with specific rRNA sequences and snoRNAs. These findings suggest that Dbp6's activities are important for proper rRNA folding and snoRNA interactions.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Julia Contreras, Oscar Ruiz-Blanco, Carine Dominique, Odile Humbert, Yves Henry, Anthony K. Henras, Jesus de la Cruz, Eduardo Villalobo
Summary: Ribosome synthesis involves various protein trans-acting factors, including DEx(D/H)-box helicases, such as Dbp7. Dbp7 is an RNA helicase that regulates the base-pairing between snR190 small nucleolar RNA and ribosomal RNA during early ribosome biogenesis. The N- and C-terminal domains of Dbp7 are important for its nuclear import, normal growth, and 60S ribosomal subunit synthesis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Christophe Papin, Abdulkhaleg Ibrahim, Jamal S. M. Sabir, Stephanie Le Gras, Isabelle Stoll, Raed S. Albiheyri, Ali T. Zari, Ahmed Bahieldin, Alfonso Bellacosa, Christian Bronner, Ali Hamiche
Summary: Our study demonstrates the important role of MBD4 protein in DNA methylation maintenance and G/T mismatch repair. Transcriptome and methylome analyses reveal a widespread decrease in methylation of promoters, gene bodies, and repetitive elements in the absence of MBD4. Loss of methylation marks leads to broad transcriptional derepression, affecting promoters and retroelements with low methylated CpG density. MBD4 forms a complex with mismatch repair proteins and exhibits high glycosylase/AP-lyase endonuclease activity towards methylated DNA substrates containing a G/T mismatch. The association of MBD4 with MLH1 is required for this activity.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)