Article
Medicine, Research & Experimental
Guofang Lu, Siyuan Tian, Yi Sun, Jiaqiang Dong, Na Wang, Jiaoxia Zeng, Yongzhan Nie, Kaichun Wu, Ying Han, Bin Feng, Yulong Shang
Summary: Inflammatory stimuli in the tumor microenvironment play vital roles in cancer progression, with the mechanism of inflammation-induced cancer metastasis in gastric cancer still poorly understood. NEK9 directly regulates cell motility and RhoA activation in gastric cancer by phosphorylating ARHGEF2. The IL-6-mediated suppression of miR-520f-3p leads to an increase in NEK9, GP130, and STAT3 levels, contributing to reduced overall survival of GC patients. Targeting the IL-6-STAT3-NEK9 pathway may offer a new strategy for treating gastric cancer.
Article
Multidisciplinary Sciences
Tamas Szaniszlo, Mate Fulop, Matyas Pajkos, Gabor Erdos, Reka Agnes Kovacs, Henrietta Vadaszi, Jozsef Kardos, Zsuzsanna Dosztanyi
Summary: The study characterized the interaction between Dynein light chain LC8 and centrosomal protein LCA5, revealing that LC8 acts as an oligomerization engine in the formation of oligomers of LCA5.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Yasuhiro Yamamoto, Haruka Chino, Satoshi Tsukamoto, Koji L. Ode, Hiroki R. Ueda, Noboru Mizushima
Summary: This study demonstrates that NEK9 interacts with MYH9 to regulate ciliogenesis, with NEK9's LIR playing a key role in the autophagic degradation of MYH9. This interaction may have adaptive implications for terrestrial life, given the conservation of NEK9's LIR only in land vertebrates.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Hannah R. Bridges, James N. Blaza, Zhan Yin, Injae Chung, Michael N. Pollak, Judy Hirst
Summary: We have characterized the molecular mode of action of biguanides by studying the drug-target interaction with cryo-electron microscopy and enzyme kinetics. Our results explain the selectivity of biguanide binding to different enzyme states and provide a structural basis for their action. This research also opens new opportunities for the rational design of medicinal biguanides.
Article
Multidisciplinary Sciences
Mengmeng Wang, Jing-Xiang Wu, Dian Ding, Lei Chen
Summary: This study presents the structures of pancreatic K-ATP channel and reveals the mechanism of nucleotide regulation.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lilei Xu, Yu Xiao, Jie Zhang, Xianyang Fang
Summary: In bacteria, the expression of folate-related genes is controlled by different types of riboswitches, including the THF-I and recently discovered THF-II riboswitches. In this study, the crystal structures of THF-II riboswitch from Mesorhizobium loti were determined, revealing a unique architecture stabilized by continuous base pair stacking. The ligand binding pocket of the riboswitch accommodates the pterin moiety and its binding is influenced by Mg2+ ions. Ligand binding reduces accessibility of the ribosome binding site, regulating the expression of downstream genes. These findings provide mechanistic insights into translation regulation by THF-II riboswitch.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biology
Sensen Zhang, Jun Zhou, Yuebin Zhang, Tianya Liu, Perrine Friedel, Wei Zhuo, Suma Somasekharan, Kasturi Roy, Laixing Zhang, Yang Liu, Xianbin Meng, Haiteng Deng, Wenwen Zeng, Guohui Li, Biff Forbush, Maojun Yang
Summary: In this study, the cryo-electron microscopy structures of the two neuronal cation-chloride cotransporters human NKCC1 and mouse KCC2 were presented, identifying essential residues for ion transport. The study proposes mechanisms by which phosphorylation regulates the activity of these cation-chloride cotransporters.
COMMUNICATIONS BIOLOGY
(2021)
Article
Immunology
Yi Zhong, Sarah K. Walker, Yuri Pritykin, Christina S. Leslie, Alexander Y. Rudensky, Joris van der Veeken
Summary: Zhong et al. studied the transcriptional regulation of T cell gene expression upon viral challenge using B6/Cast F1 hybrid mice. They found that members of Ets, Runx, and TCF/Lef transcription factor families play key roles in maintaining or increasing chromatin accessibility during T cell activation. Some highly induced immune response genes exhibit a noncanonical TF recruitment pattern.
Article
Multidisciplinary Sciences
Hayarpi Torosyan, Michael D. Paul, Antoine Forget, Megan Lo, Devan Diwanji, Krzysztof Pawlowski, Nevan J. Krogan, Natalia Jura, Kliment A. Verba
Summary: In this study, the cryo-EM structure of the PEAK3/14-3-3 complex was presented, revealing the asymmetric binding mode and the unique secondary interaction between PEAK3 and 14-3-3. It was also found that PKD regulates the binding of PEAK3 and 14-3-3, and disruption of this binding leads to nuclear enrichment of PEAK3 and distinct protein-protein interactions. The results demonstrate how 14-3-3 modulates PEAK3 localization and protein-protein interactions.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Julian F. Ehrmann, Daniel B. Grabarczyk, Maria Heinke, Luiza Deszcz, Robert Kurzbauer, Otto Hudecz, Alexandra Shulkina, Rebeca Gogova, Anton Meinhart, Gijs A. Versteeg, Tim Clausen
Summary: Inhibitor of apoptosis proteins (IAPs) bind to pro-apoptotic proteases, keeping them inactive and preventing cell death. The atypical ubiquitin ligase BIRC6 is the only essential IAP, additionally functioning as a suppressor of autophagy. Cryo-electron microscopy structures showed that BIRC6 forms a megadalton crescent shape that arcs around a spacious cavity containing receptor sites for client proteins. Multivalent binding of SMAC obstructs client binding, impeding ubiquitination of both autophagy and apoptotic substrates. Based on these data, we discuss how the BIRC6/SMAC complex can act as a stress-induced hub to regulate apoptosis and autophagy drivers.
Article
Multidisciplinary Sciences
Jun Yu, Pierre Raia, Chloe M. Ghent, Tobias Raisch, Yashar Sadian, Simone Cavadini, Pramod M. Sabale, David Barford, Stefan Raunser, David O. Morgan, Andreas Boland
Summary: The structures of separase in complex with either securin or cyclin B-CDK1 reveal the diverse array of mechanisms by which they bind and inhibit separase, shedding light on the regulation of chromosome separation during the cell cycle.
Article
Cell Biology
Yeonghyeon Lee, Jaejin Kim, Mi-Sung Kim, Yoojin Kwon, Sanghee Shin, Hyerim Yi, Hyeonkyeong Kim, Moon Jong Chang, Chong Bum Chang, Seung-Baik Kang, V. Narry Kim, Jin-Hong Kim, Jong-Seo Kim, Stephen J. Elledge, Chanhee Kang
Summary: Autophagy plays a caretaker role in cellular senescence by regulating protein stability, coordinating multiple regulatory components, limiting specific proteins to ameliorate proteotoxic stress, promoting redox homeostasis, and enhancing inflammation. This highlights the intertwined relationship between two important age-related processes.
DEVELOPMENTAL CELL
(2021)
Article
Biochemistry & Molecular Biology
Toru Sengoku, Masaaki Shiina, Kae Suzuki, Keisuke Hamada, Ko Sato, Akiko Uchiyama, Shunsuke Kobayashi, Asako Oguni, Hayato Itaya, Kota Kasahara, Hirotomo Moriwaki, Chiduru Watanabe, Teruki Honma, Chikako Okada, Shiho Baba, Tsutomu Ohta, Hozumi Motohashi, Masayuki Yamamoto, Kazuhiro Ogata
Summary: This study reveals the crystal structures of Nrf2/NFE2L2, a CNC family protein, in complex with MafG and CsMBE. The CNC motif restricts the conformation of crucial amino acids, leading to enhanced DNA binding affinity. The CNC-sMaf heterodimer competes with the sMaf homodimer on target genes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Hongmiao Hu, Anne-Marie M. van Roon, George E. Ghanim, Bilal Ahsan, Abraham O. Oluwole, Sew-Yeu Peak-Chew, Carol V. Robinson, Thi Hoang Duong Nguyen
Summary: Shelterin and nucleosomes interact at mammalian telomeres, but the mechanism is not yet understood. Cryo-electron microscopy was used to study the structure of a human telomeric nucleosome bound to the shelterin factor TRF1. The study revealed that TRF1 binds to unwrapped nucleosomal DNA ends by engaging both the DNA and the histone octamer, resulting in a shift in the nucleosomal DNA. Phosphorylation of TRF1 and a noncanonical DNA binding surface on TRF1 were found to be crucial for its association with telomeric nucleosomes. These findings provide important insights into shelterin-chromatin interactions and its roles at telomeres.
Article
Biochemistry & Molecular Biology
Lu Chen, Yanan Zhang, Xin Shu, Qiong Chen, Tiantian Wei, Heman Wang, Xiaorong Wang, Qirou Wu, Xiaomei Zhang, Xiaoyan Liu, Suya Zheng, Lan Huang, Junyu Xiao, Chao Jiang, Bing Yang, Zhiping Wang, Xing Guo
Summary: This study identified a novel mechanism involved in the spatial regulation of proteasome function by phosphorylation, providing new insights into anticancer therapies based on tyrosine kinase inhibitors.
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)
Correction
Multidisciplinary Sciences
Ricardo Sant'Anna, Pablo Gallego, Lei Z. Robinson, Alda Pereira-Henriques, Nelson Ferreira, Francisca Pinheiro, Sebastian Esperante, Irantzu Pallares, Oscar Huertas, Maria Rosario Almeida, Natalia Reixach, Raul Insa, Adrian Velazquez-Campoy, David Reverter, Nuria Reig, Salvador Ventura
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Hector Lopez-Laguna, Ariana Rueda, Carlos Martinez-Torro, Lucia Sanchez-Alba, Jose Vicente Carratala, Jan Atienza-Garriga, Eloi Parlade, Julieta M. Sanchez, Naroa Serna, Eric Volta-Duran, Neus Ferrer-Miralles, David Reverter, Ramon Mangues, Antonio Villaverde, Esther Vazquez, Ugutz Unzueta
Summary: We have developed a novel protein assembly method based on a histidine-templated cysteine-coupling concept, which enables the spontaneous and efficient self-assembly of tagged proteins into monodisperse nanoparticles. This method can be used for one-step IMAC-based protein purification and for the formation of higher-order microparticulate materials as nanoparticle-releasing protein-only depots. The green biofabrication concept proposed here offers wide applicability for the further development of clinically usable protein materials.
ACS SUSTAINABLE CHEMISTRY & ENGINEERING
(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
Multidisciplinary Sciences
Nuria Gallisa-Sune, Paula Sanchez-Fernandez-de-Landa, Fabian Zimmermann, Marina Serna, Laura Regue, Joel Paz, Oscar Llorca, Jens Luders, Joan Roig
Summary: This study demonstrates that the adaptor protein BICD2 is activated through phosphorylation, which promotes the formation of the dynein motor complex and regulates its localization and activity within cells. This finding is crucial for understanding the functional importance of dynein in both dividing and non-dividing cells.
NATURE COMMUNICATIONS
(2023)
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
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
Endocrinology & Metabolism
Laura Regue, William Wang, Fei Ji, Joseph Avruch, Hua Wang, Ning Dai
Summary: IMP2 gene plays a crucial role in adipocyte development by promoting early commitment of adipocyte-derived stem cells into preadipocytes. It is also essential for maintaining white adipose tissue homeostasis. However, its contribution to insulin resistance, a major risk factor for T2D, is not clear.
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.
Article
Biochemistry & Molecular Biology
Cristina Sarasa-Buisan, Etienne Emonot, Marta Martinez-Julvez, Emma Sevilla, Adrian Velazquez-Campoy, Serge Crouzy, M. Teresa Bes, Isabelle Michaud-Soret, Maria F. Fillat
Summary: Metal and redox homeostasis in cyanobacteria is tightly controlled by the FUR proteins. This study focuses on the characterization of the FurC protein in Anabaena sp. PCC7120 and reveals its involvement in metal and redox regulation. The study provides insights into the mechanisms of FurC and the reversible inactivation of the protein through disulfide bonds and metal catalyzed oxidation.
Article
Biochemistry & Molecular Biology
Miguel A. Casado-Combreras, Francisco Rivero-Rodriguez, Carlos A. Elena-Real, Dmitry Molodenskiy, Antonio Diaz-Quintana, Marlene Martinho, Guillaume Gerbaud, Katiuska Gonzalez-Arzola, Adrian Velazquez-Campoy, Dmitri Svergun, Valerie Belle, Miguel A. De la Rosa, Irene Diaz-Moreno
Summary: Intrinsic protein flexibility is crucial for the adaptability and recognition of complexes. This study reveals that the flexible region of the protein SET/TAF-I beta can activate PP2A by interacting with cytochrome c in a dynamic manner.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)