Article
Immunology
Xin Zhang, Siting Wu, Zetian Liu, Hong Chen, Jiaming Liao, Jingguang Wei, Qiwei Qin
Summary: In this study, the researchers cloned and characterized the RIP2 homolog from orange-spotted grouper (EcRIP2) and investigated its role in fish DNA virus infection. They found that EcRIP2 could inhibit the replication of SGIV and suppress the expression of inflammatory factors by competing with EcASC for binding EcCaspase-1. This study provides new insights into the modulatory mechanism of the RIP2-associated pathway and RIP2-mediated fish diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yue-Xuan Wang, Sui-Feng Xu, Ye-Wen Wang, Yun-Xiang Jiang, Qi-Wei Qin, Shi-Na Wei
Summary: This study aimed to investigate the protective effect of curcumin against Singapore grouper iridovirus-induced intestinal damage in orange-spotted groupers. The results showed that curcumin significantly alleviated intestine damage, repaired intestinal barrier dysfunction, suppressed intestinal cells apoptosis and inflammatory response, protected intestinal cells from oxidative injury, and restored the disruption of the intestinal microbiota caused by the virus. These findings provide a theoretical basis for the use of curcumin in aquaculture to prevent SGIV-induced intestinal injury.
Article
Fisheries
Yuexuan Wang, Suifeng Xu, Chengzong Han, Liqun Wang, Qi Zheng, Shaowen Wang, Youhua Huang, Shina Wei, Qiwei Qin
Summary: SGIV infection, a major cause of mortality and economic losses in grouper aquaculture industry, can be effectively inhibited by curcumin through multiple antiviral mechanisms both in vitro and in vivo. Curcumin impairs attachment of SGIV virion and regulates cellular immune and inflammatory responses related to the NF-kappa B signaling pathway. Additionally, curcumin plays a critical role in preventing SGIV infection through enhancing antioxidant capacity via the Nrf2/Keap1 signaling pathway. This study highlights the potential of curcumin as a candidate drug for treating SGIV infection.
Article
Fisheries
Jiaxin Liu, Xinyue Zhang, Jiaying Zheng, Yepin Yu, Xiaohong Huang, Jingguang Wei, Omar Mukama, Shaowen Wang, Qiwei Qin
Summary: Iridoviruses are known to cause serious diseases in fish species worldwide. Singapore grouper iridovirus (SGIV) has caused significant economic losses in grouper aquaculture without effective therapies. A novel LFB combined with DNA aptamers has been developed for rapid and sensitive detection of SGIV infection, showing high specificity and sensitivity in vitro and in vivo.
Article
Fisheries
Minglan Guo, Jingguang Wei, Yongcan Zhou, Qiwei Qin
Summary: In this study, a protein called EcMKP-1 was cloned and found to play a critical role in combating Singapore grouper iridovirus (SGIV) infection. It regulates the host's immune response and suppresses viral replication. The results demonstrate the important functions of EcMKP-1 in antiviral immunity, JNK dephosphorylation, and anti-apoptosis during SGIV infection.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2023)
Article
Fisheries
Jinpeng Chen, Liqun Wang, Jianling Huang, Xinshuai Li, Lingfeng Guan, Qing Wang, Min Yang, Qiwei Qin
Summary: This study cloned and characterized a novel type of MHC-I genotype, named EcMHC-IA*01, which plays an important role in antiviral immune response and apoptosis in fish.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Fisheries
Yuexuan Wang, Suifeng Xu, Yewen Wang, Xuchao Zhang, Jiatao Chen, Qiwei Qin, Shina Wei
Summary: This study found that curcumin, extracted from the traditional Chinese medicine turmeric, has various biological activities, including immunoenhancement, antioxidant, and antibacterial properties. The results showed that curcumin can enhance fish immunity, reduce mortality caused by viral infection, and repair liver injury caused by the virus. This provides a theoretical foundation for the functional development of curcumin in aquaculture.
Article
Fisheries
Yuexuan Wang, Suifeng Xu, Chengzong Han, Youhua Huang, Jingguang Wei, Shina Wei, Qiwei Qin
Summary: The molecular mechanism of curcumin against SGIV infection mainly includes suppressing cell apoptosis, inhibiting related signaling pathways, and promoting autophagy.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Fisheries
Xia Liang, Junjia Liang, Jinqiao Cao, Shijia Liu, Quan Wang, Yunshang Ning, Zengjian Liang, Jiaying Zheng, Zemiao Zhang, Jiayi Luo, Yingjing Chen, Xiaohong Huang, Yan Huang, Qiwei Qin, Sheng Zhou
Summary: In this study, Bacillus subtilis spores were used as a vehicle to display the VP19 protein on their surface, and orally vaccinated grouper showed improved survival rate and lower viral load compared to the control group. The specific IgM levels and immune-related gene expression also indicated activated immune responses in the vaccinated group. This study provided a feasible strategy for controlling fish virus diseases.
FISH & SHELLFISH IMMUNOLOGY
(2023)
News Item
Biochemistry & Molecular Biology
Kanishk Jain, Brian D. Strahl
Summary: High-throughput biochemical and biological analyses of disease-associated histone mutations reveal key residues in globular cores that affect chromatin remodeling, nucleosome stability, and stem cell pluripotency.
NATURE CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Weihua Qin, Enes Ugur, Christopher B. Mulholland, Sebastian Bultmann, Irina Solovei, Miha Modic, Martha Smets, Michael Wierer, Ignasi Forne, Axel Imhof, M. Cristina Cardoso, Heinrich Leonhardt
Summary: In this study, it was found that HP1β is phosphorylated by CK2 during stem cell differentiation, leading to binding with KAP1 and sequestration of KAP1 in heterochromatin compartments, resulting in downregulation of pluripotency factors and triggering pluripotency exit.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Mariola Ferreras-Gutierrez, Belen Chaves-Arquero, Amaia Gonzalez-Magana, Nekane Merino, Ignacio Amusategui-Mateu, Sonia Huecas, Francisco J. Medrano, Francisco J. Blanco
Summary: Proteins of the ING family regulate chromatin transcription by recruiting remodeling complexes to sites with H3K4me3 modification. ING3, an oncoprotein, facilitates histone acetylation and forms homodimers with an antiparallel coiled-coil fold. The crystal structure of ING3's PHD domain reveals its interaction with H3K4me3 and the impact of mutations on histone recognition.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Fisheries
Luhao Zhang, Shaozhu Kang, Hong Chen, Jiaming Liao, Mengshi Sun, Siting Wu, Zhuqing Xu, Linting Xu, Xin Zhang, Qiwei Qin, Jingguang Wei
Summary: In this study, a TAK1 homolog, HgTAK1, was cloned from hybrid grouper. HgTAK1 was found to be upregulated after viral infection and promoted viral replication while inhibiting the activation of NF-kappa B and ISRE. HgTAK1 also interacted with IRF3 and IRF7.
FISH & SHELLFISH IMMUNOLOGY
(2022)
Article
Fisheries
Linting Xu, Mengke Liu, Hong Chen, Luhao Zhang, Qiongyue Xu, Zhouling Zhan, Zhuqing Xu, Shaoli Liu, Siting Wu, Xin Zhang, Qiwei Qin, Jingguang Wei
Summary: In this study, a protein encoded by SGIV ORF122, VP122, has been identified, which promotes SGIV replication and inhibits the immune response by targeting EcSTING. This interaction inhibits the self-interaction of EcSTING, but has no effect on the recruitment of other immune-related proteins. These findings highlight the crucial role of VP122 in modulating the host-virus interaction.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
David Dilworth, Ronan P. Hanley, Renato Ferreira de Freitas, Abdellah Allali-Hassani, Mengqi Zhou, Naimee Mehta, Matthew R. Marunde, Suzanne Ackloo, Raquel Arminda Carvalho Machado, Aliakbar Khalili Yazdi, Dominic D. G. Owens, Victoria Vu, David Y. Nie, Mona Alqazzaz, Edyta Marcon, Fengling Li, Irene Chau, Albina Bolotokova, Su Qin, Ming Lei, Yanli Liu, Magdalena M. Szewczyk, Aiping Dong, Sina Kazemzadeh, Tigran Abramyan, Irina K. Popova, Nathan W. Hall, Matthew J. Meiners, Marcus A. Cheek, Elisa Gibson, Dmitri Kireev, Jack F. Greenblatt, Michael-C Keogh, Jinrong Min, Peter J. Brown, Masoud Vedadi, Cheryl H. Arrowsmith, Dalia Barsyte-Lovejoy, Lindsey James, Matthieu Schapira
Summary: NSD2 is an enzyme responsible for dimethylation of lysine 36 of histone 3, with multiple domains involved in chromatin reading. The chemical probe UNC6934 can modulate NSD2 activity and localization, affecting cellular functions.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Maria Conde-Gimenez, Juan Jose Galano-Frutos, Maria Galiana-Cameo, Alejandro Mahia, Bruno L. Victor, Sandra Salillas, Adrian Velazquez-Campoy, Rui M. M. Brito, Jose Antonio Galvez, Maria D. Diaz-de-Villegas, Javier Sancho
Summary: This study designs a new generation of compounds with higher affinity for phenylalanine hydroxylase (PAH) using alchemical free energy calculations. These compounds show greater stabilizing effect and bind tighter to the enzyme compared to the lead compound IV. The correspondence between calculated and experimentally determined values supports the use of this method to design pharmacological chaperones for PKU treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Microbiology
Andres Gonzalez, Javier Casado, Miyase Goezde Gunduz, Brisa Santos, Adrian Velazquez-Campoy, Cristina Sarasa-Buisan, Maria F. Fillat, Milagrosa Montes, Elena Piazuelo, Angel Lanas
Summary: This study found that certain 1,4-dihydropyridine (DHP) drugs can be effective bactericidal agents against antibiotic-resistant strains of the gastric carcinogenic bacterium Helicobacter pylori. Twelve novel DHP derivatives exhibited strong antibacterial activities, specifically targeting H. pylori regulator HsrA and inhibiting its DNA binding. These derivatives showed no deleterious effects on Escherichia coli and Staphylococcus epidermidis. The findings suggest the potential for structure-based design of novel anti-H. pylori drugs.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Srihari Shankar, Sarath Ramachandran, Nikhil Tulsian, Sridhar Radhakrishnan, Chacko Jobichen, J. Sivaraman
Summary: Glutaminase is a metabolic enzyme that plays a role in cancer cell proliferation. A new allosteric site has been identified in the enzyme, which can be targeted to develop specific inhibitors for the treatment of cancer.
Article
Biochemistry & Molecular Biology
Jose L. Neira, Bruno Rizzuti, Salome Araujo-Abad, Olga Abian, Maria Esther Farez-Vidal, Adrian Velazquez-Campoy, Camino de Juan Romero
Summary: This study describes the interaction between PKP1 and PADI4 and provides insights into their binding mode and binding hot-spot. This is of importance for understanding tumor development and the formation of neutrophil extracellular traps.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2023)
Article
Biochemistry & Molecular Biology
David Ortega-Alarcon, Rafael Claveria-Gimeno, Sonia Vega, Olga C. Jorge-Torres, Manel Esteller, Olga Abian, Adrian Velazquez-Campoy
Summary: Hydroxymethylated cytosine (5hmC) is a stable DNA epigenetic mark that interacts with MeCP2 in a distinct mode with a specific thermodynamic signature. Mutations associated with Rett syndrome alter the interaction between MeCP2 and dsDNA in a cytosine modification-specific manner, which may be correlated with disease onset time and clinical severity score.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Jianwei Li, Chacko Jobichen, Satoru Machida, Sun Meng, Randy J. Read, Hongying Chen, Shi Jian, Yuren Adam Yuan, J. Sivaraman
Summary: This study reports the crystal structures of apo Cas12a from Lachnospiraceae bacterium MA2020 (Lb2) and the Lb2Cas12a+crRNA complex, as well as the cryo-EM structure and functional studies of the Lb2Cas12a+crRNA+DNA complex. The findings reveal the unique conformations and structural rearrangements of Lb2 Cas12a in different complexes, as well as the conformational changes in specific domains to facilitate the recognition and cleavage of target DNA. These results provide valuable insights into the mechanism of crRNA recognition and DNA cleavage by Cas12a.
Article
Multidisciplinary Sciences
Jorge Lozano-Juste, Lourdes Infantes, Irene Garcia-Maquilon, Rafael Ruiz-Partida, Ebe Merilo, Juan Luis Benavente, Adrian Velazquez-Campoy, Alberto Coego, Mar Bono, Javier Forment, Begona Pampin, Paolo Destito, Adrian Monteiro, Ramon Rodriguez, Jacobo Cruces, Pedro L. Rodriguez, Armando Albert
Summary: Through structure-based targeted design, a chemical-genetic orthogonal approach was used to generate an ABA receptor agonist molecule (iSB09) and engineer a CsPYL1 ABA receptor, named CsPYL1(5m), which efficiently binds iSB09. This optimized receptor-agonist pair leads to activation of ABA signaling and significant improvement in drought tolerance.
Article
Oncology
Sonia Hermoso-Duran, Maria Jose Domper-Arnal, Pilar Roncales, Sonia Vega, Oscar Sanchez-Gracia, Jorge L. L. Ojeda, Angel Lanas, Adrian Velazquez-Campoy, Olga Abian
Summary: The aim of this study was to investigate the interference of colonoscopy bowel preparation on the results of thermal liquid biopsy (TLB). The results showed that bowel preparation altered serum protein levels, affected TLB parameters, and may compromise the diagnostic capability of other liquid-biopsy-based methods. Therefore, blood extraction after bowel preparation for colonoscopy should be avoided.
Article
Chemistry, Medicinal
Maria Nuria Peralta-Moreno, Vanessa Anton-Munoz, David Ortega-Alarcon, Ana Jimenez-Alesanco, Sonia Vega, Olga Abian, Adrian Velazquez-Campoy, Timothy M. Thomson, Jose Manuel Granadino-Roldan, Claudia Machicado, Jaime Rubio-Martinez
Summary: Since the outbreak of the COVID-19 pandemic, there have been over 750 million reported cases of COVID-19 caused by SARS-CoV-2. In order to find effective treatments, intensive research has been conducted on therapeutic agents derived from pharmaceutical repositioning or natural products. This study focuses on identifying inhibitors for the SARS-CoV-2 M-pro main protease dimer using virtual screening of natural compounds derived from Peruvian flora. The compound Hyperoside displayed inhibitory activity against M-pro in vitro, with a K-i value lower than 20 μM, possibly through allosteric modulation.
Article
Biochemistry & Molecular Biology
Salome Araujo-Abad, Bruno Rizzuti, Adrian Villamarin-Ortiz, David Pantoja-Uceda, Celia M. Moreno-Gonzalez, Olga Abian, Adrian Velazquez-Campoy, Jose L. Neira, Camino de Juan Romero
Summary: PADI4 and MDM2 were found to interact in the nucleus and cytosol of various cancer cell lines, and this binding was inhibited by GSK484. Further experiments revealed that the N-terminal region of MDM2 interacted with PADI4, and certain amino acid residues were affected by the enzyme. This finding suggests potential therapeutic value in utilizing MDM2 citrullination to improve cancer treatment.
Article
Biochemistry & Molecular Biology
Qingqing Huang, Edem Gavor, Nikhil Kumar Tulsian, Jingsong Fan, Qingsong Lin, Yu Keung Mok, R. Manjunatha Kini, J. Sivaraman
Summary: The pupal cuticle protein from Aedes aegypti (AaPC) inhibits dengue virus (DENV) infection by directly binding to and causing the aggregation of the virus, as well as by potentially influencing viral recognition and attachment through interaction with human immune receptors.
Article
Chemistry, Multidisciplinary
Sunil Singh, Satoru Machida, Nikhil Kumar Tulsian, Yeu Khai Choong, Joel Ng, Srihari Shankar, Yaochen Liu, Krisha Vashdev Chandiramani, Jian Shi, J. Sivaraman
Summary: The authors present the cryo-EM structures of human HACE1 and provide insights into how the enzymatic activity of HACE1 is regulated. The study reveals the role of the MID domain in substrate recognition.
Article
Multidisciplinary Sciences
Margarida Bastos, Olga Abian, Christopher M. Johnson, Frederico Ferreira-da-Silva, Sonia Vega, Ana Jimenez-Alesanco, David Ortega-Alarcon, Adrian Velazquez-Campoy
Summary: Isothermal titration calorimetry (ITC) has become the gold standard for studying molecular interactions in solution. It is widely used for characterizing molecular interactions between ligands and macromolecules. This Primer provides an overview of ITC's foundations, instrumentation, common applications, extensions and modifications, advantages and caveats, as well as recent and future developments.
NATURE REVIEWS METHODS PRIMERS
(2023)
Article
Biochemistry & Molecular Biology
Bruno Rizzuti, Olga Abian, Adrian Velazquez-Campoy, Jose L. Neira
Summary: This study investigates the stability and conformational features of the N-terminal region of MDM2, revealing the low stability and unfolding intermediates of this region. The low stability of this protein may be related to its inherent flexibility and ability to interact with multiple molecular partners.
Article
Multidisciplinary Sciences
Nerea Novo, Silvia Romero-Tamayo, Carlos Marcuello, Sergio Boneta, Irene Blasco-Machin, Adrian Velazquez-Campoy, Raquel Villanueva, Raquel Moreno-Loshuertos, Anabel Lostao, Milagros Medina, Patricia Ferreira
Summary: AIF is a moonlighting flavoenzyme that is involved in the assembly of mitochondrial respiratory complexes in healthy cells but can also trigger DNA cleavage and cell death. This study demonstrates the molecular assembly of a DNA-degradosome complex involving AIF, CypA, and histone H2AX, and the cooperative effects of these components in degrading genomic DNA. Additionally, the study reveals that AIF possesses nuclease activity that is stimulated by the presence of Mg2+ or Ca2+, which allows it to efficiently degrade genomic DNA alone or in cooperation with CypA. It is also found that the TopIB and DEK motifs in AIF are responsible for its nuclease activity. These findings enhance our understanding of AIF's role in promoting apoptosis and provide potential avenues for the development of new therapeutic strategies.
