Article
Chemistry, Multidisciplinary
Julie M. Garlick, Steven M. Sturlis, Paul A. Bruno, Joel A. Yates, Amanda L. Peiffer, Yejun Liu, Laura Goo, LiWei Bao, Samantha N. De Salle, Giselle Tamayo-Castillo, Charles L. Brooks, Sofia D. Merajver, Anna K. Mapp
Summary: Inhibitors of transcriptional protein-protein interactions have high value for both tools and therapeutic applications. This study demonstrates that norstictic acid, a depsidone natural product, blocks Med25-transcriptional activator PPIs through an alternative binding site, providing opportunities for inhibitor discovery in challenging proteins with structurally dynamic loops.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Srinivasan Rengachari, Sandra Schilbach, Shintaro Aibara, Christian Dienemann, Patrick Cramer
Summary: Mediator is a conserved coactivator complex involved in the regulated initiation of transcription at eukaryotic genes. It interacts with transcriptional activators to stimulate RNA polymerase II phosphorylation and promoter escape. The complex structure involves various modules that can affect the activity conformation of CDK7 kinase.
Article
Biochemistry & Molecular Biology
Koji Kawasaki, Takashi Fukaya
Summary: This study provides evidence that the dynamic assembly and disassembly process of transcription factor (TF) clusters at enhancers is a major source of transcriptional bursting in developing Drosophila embryos. The regulatory connectivity between TF clustering and burst induction is highly regulated through intrinsically disordered regions (IDRs). The study also visualizes the presence of shared TF clusters during the co-activation of two distant genes, providing a concrete molecular explanation for the newly proposed topological operon hypothesis in metazoan gene regulation.
Article
Biochemistry & Molecular Biology
Max Staller, Eddie Ramirez, Sanjana R. Kotha, Alex S. Holehouse, Rohit Pappu, Barak A. Cohen
Summary: The study investigated acidic activation domains by designing thousands of variants, and found that strong activation domain activity requires a balance between the number of acidic residues, aromatic and leucine residues. A predictor was developed to identify and accurately predict acidic activation domains.
Article
Biochemistry & Molecular Biology
Min-Sung Lee, Sang-Ok Lee, Joonhyeok Choi, Minju Ryu, Mi-Kyung Lee, Ji-Hun Kim, Eunha Hwang, Chong-Kil Lee, Seung-Wook Chi, Kyoung-Seok Ryu
Summary: The RING domain of MUL1 mediates the ubiquitylation of the p53-transactivation domain. The study reveals the mechanism underlying the simultaneous recruitment of UBE2D2 and the substrate TAD(p53) by RING(MUL1). It was found that RING(MUL1) binding induced a closed conformation of UBE2D2 and accelerated its hydrolysis. Additionally, the binding affinity of TAD(p53) was enhanced by the complex formation of RING(MUL1) and UBE2D2.
Article
Biochemistry & Molecular Biology
Federica Nicolini, Toni Todorovski, Eduard Puig, Mireia Diaz-Lobo, Marta Vilaseca, Jesus Garcia, David Andreu, Ernest Giralt
Summary: Tumour suppressor p53 plays a crucial role in cancer development, but the tetramerisation mechanism of p53 is not fully understood. Mutations in p53, which occur in nearly 50% of cancers, can alter the oligomeric state of the protein and affect its biological function and cell fate decisions.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Article
Cell Biology
Jacques Behmoaras, Jesus Gil
Summary: Cellular senescence is a program that prevents the replication of old, damaged, or cancerous cells and produces bioactive secretome. Senescent cells and macrophages interact with each other, sharing multiple phenotypic characteristics, and eliminating senescent cells results in widespread benefits.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Chemistry, Physical
Victor A. Prieto, Kevin E. W. Namitz, Scott A. Showalter
Summary: This study examines the interactions mediated by charged residues in intrinsically disordered protein sequences, specifically focusing on the role of charged regions in the binding between Fcp1 and its partner Rap74. The experimental results show both intramolecular and intermolecular interactions between oppositely charged regions in Fcp1, with hydrophobic interactions playing a key role in the formation of the complex. Mutations in charged residues support the hypothesis that they contribute to the strength of binding, as evidenced by paramagnetic relaxation enhancement data.
JOURNAL OF PHYSICAL CHEMISTRY B
(2021)
Article
Biochemistry & Molecular Biology
Masahiko Okuda, Tetsufumi Suwa, Hidefumi Suzuki, Yuki Yamaguchi, Yoshifumi Nishimura
Summary: This study reveals that the shared N-terminal tail (NTT) of the common subunit RPB6 in all three eukaryotic RNA polymerases interacts with the PH domain (PH-D) of the p62 subunit of TFIIH, playing crucial roles in transcription and nucleotide excision repair.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Qilin Xie, Kota Kasahara, Junichi Higo, Takuya Takahashi
Summary: This study investigated the effects of phosphorylation on the function of PC4 using enhanced molecular dynamics simulation. The results showed that phosphorylation significantly weakened the interaction between PC4 and VP16ad, leading to the formation of a compact structure in the IDR. This study is important for computational elucidation of the functional modulation of PC4.
Article
Multidisciplinary Sciences
Simone A. Thair, Yudong D. He, Yehudit Hasin-Brumshtein, Suraj Sakaram, Rushika Pandya, Jiaying Toh, David Rawling, Melissa Remmel, Sabrina Coyle, George N. Dalekos, Ioannis Koutsodimitropoulos, Glykeria Vlachogianni, Eleni Gkeka, Eleni Karakike, Georgia Damoraki, Nikolaos Antonakos, Purvesh Khatri, Evangelos J. Giamarellos-Bourboulis, Timothy E. Sweeney
Summary: The study compared the gene expression changes in COVID-19 patients with non-COVID-19 viral infections and identified 416 genes specific to COVID-19. It also found that in COVID-19, the proportions of CD56(bright) natural killer cells and M2 macrophages increased, providing insights into the pathophysiology of the host response to SARS-CoV-2.
Article
Cell Biology
Tiphaine Douanne, Jane C. Stinchcombe, Gillian M. Griffiths
Summary: Immune synapses play a crucial role in communication and immune response coordination among immune cells, bearing resemblance to cellular structures responsible for signaling and secretion. Studies have revealed morphological, functional, and molecular similarities between immune synapses and primary cilia, with ongoing comparative research shedding light on their underlying molecular mechanisms.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fengyan Han, Lei Zhang, Shaoxia Liao, Yanmin Zhang, Lili Qian, Feijun Hou, Jingwen Gong, Maode Lai, Honghe Zhang
Summary: Protein nucleocytoplasmic transport is disrupted in cancer cells, with the S100A2/KPNA2 complex playing a key role in promoting the nuclear transportation of the tumor-associated transcription factor NFYA in colorectal cancer. Inhibiting the binding sites of S100A2/KPNA2 with a specific inhibitor, delanzomib, may be a potential therapeutic approach for CRC by inhibiting the transcriptional activity of E-cadherin and preventing CRC metastasis.
Article
Biochemistry & Molecular Biology
Alena Hofrova, Petr Lousa, Monika Kubickova, Jozef Hritz, Tomas Otasevic, Martin Repko, Andrea Knight, Martin Piskacek
Summary: The 9aaTAD interacts with KIX through two hydrophobic regions, forming the KIX-L12-G2 region and enhancing binding. Both hydrophobic regions of 9aaTAD provide cooperative and universal binding with KIX.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Cell Biology
Dandan Zhang, Haibin Yang, Ling Jiang, Chan Zhao, Mengjun Wang, Boyi Hu, Cong Yu, Zhiyi Wei, Yu Chung Tse
Summary: The study revealed that SAO-1 binds DLC-1 to promote apoptosis and regulate CED-4/Apaf-1 accumulation in the nuclear membrane in C. elegans germ cells. It was shown through isothermal titration calorimetry and crystal structure analysis that SAO-1 interacts with DLC-1 to form a 2:4 complex. Point mutations at the SAO-1-DLC-1 binding interface hindered apoptotic corpse formation and the nuclear membrane accumulation of CED-4 in C. elegans germ cells.
CELL DEATH DISCOVERY
(2022)
Article
Biochemistry & Molecular Biology
Jennifer Roche, Eric Girard, Caroline Mas, Dominique Madern
JOURNAL OF STRUCTURAL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Mintu Chandra, Yanni K-Y Chin, Caroline Mas, J. Ryan Feathers, Blessy Paul, Sanchari Datta, Kai-En Chen, Xinying Jia, Zhe Yang, Suzanne J. Norwood, Biswaranjan Mohanty, Andrea Bugarcic, Rohan D. Teasdale, W. Mike Henne, Mehdi Mobli, Brett M. Collins
NATURE COMMUNICATIONS
(2019)
Article
Biophysics
Malene Ringkjobing Jensen, Filip Yabukarski, Guillaume Communie, Eric Condamine, Caroline Mas, Valentina Volchkova, Nicolas Tarbouriech, Jean-Marie Bourhis, Viktor Volchkov, Martin Blackledge, Marc Jamin
BIOPHYSICAL JOURNAL
(2020)
Article
Virology
Marc-Andre Hograindleur, Gregory Effantin, Daphna Fenel, Caroline Mas, Andre Lieber, Guy Schoehn, Pascal Fender, Emilie Vassal-Stermann
Article
Multidisciplinary Sciences
Jan Felix, Claire Siebert, Julia Novion Ducassou, Jerome Nigou, Pierre Simon Garcia, Angelique Fraudeau, Karine Huard, Caroline Mas, Celine Brochier-Armanet, Yohann Coute, Irina Gutsche, Patricia Renesto
Summary: This study characterized the lysine decarboxylase in F. novicida, demonstrating its involvement in oxidative stress response and identifying it as a potential drug target for survival in host cells. The research also analyzed the impact of ldcF deletion on bacterial growth under different stress conditions and in infected macrophages, revealing key proteins affected by the deletion.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Luca Signor, Theo Paris, Caroline Mas, Adrien Picard, Georges Lutfalla, Elisabetta Boeri Erba, Laure Yatime
Summary: S100A9 and S100A8 are major constituents of the S100 family of calcium-binding proteins found exclusively in vertebrates; they can act as alarmins in response to pathological conditions and have antimicrobial properties mainly through metal sequestration. The crystal structures of S100A9 reveal a canonical homodimeric form and an intramolecular disulfide bridge that stabilizes the protein's conformation, shaping a second zinc-binding site per protomer. Calcium and zinc seem to affect the relative proportion of non-covalent and covalent homodimers of S100A9.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Article
Biophysics
Blanca Lopez-Mendez, Bruno Baron, Chad A. Brautigam, Thomas A. Jowitt, Stefan H. Knauer, Stephan Uebel, Mark A. Williams, Arthur Sedivy, Olga Abian, Celeste Abreu, Malgorzata Adamczyk, Wojciech Bal, Sylvie Berger, Alexander K. Buell, Carlo Carolis, Tina Daviter, Alexander Fish, Maria Garcia-Alai, Christian Guenther, Josef Hamacek, Jitka Holkova, Josef Houser, Chris Johnson, Sharon Kelly, Andrew Leech, Caroline Mas, Daumantas Matulis, Stephen H. McLaughlin, Roland Montserret, Rouba Nasreddine, Reine Nehme, Quyen Nguyen, David Ortega-Alarcon, Kathryn Perez, Katja Pirc, Grzegorz Piszczek, Marjetka Podobnik, Natalia Rodrigo, Jasmina Rokov-Plavec, Susanne Schaefer, Tim Sharpe, June Southall, David Staunton, Pedro Tavares, Ondrej Vanek, Michael Weyand, Di Wu
Summary: Microscale thermophoresis (MST) and Temperature Related Intensity Change (TRIC) are newly developed measurement techniques used to quantify biomolecular interactions, but have not been as widely accepted as other biophysical techniques. A benchmark study was conducted to assess the reliability of MST/TRIC in characterizing biomolecular interactions, involving multiple scientific groups across Europe and the US, utilizing standardized procedures and centrally prepared samples.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Article
Biology
Dayana C. Farhat, Matthew W. Bowler, Guillaume Communie, Dominique Pontier, Lucid Belmudes, Caroline Mas, Charlotte Corrao, Yohann Coute, Alexandre Bougdour, Thierry Lagrange, Mohamed-Ali Hakimi, Christopher Swale
Summary: Proper 3' end processing of mRNAs is crucial for gene expression regulation. This study in T. gondii identifies an m6A-dependent 3'end polyadenylation acting as a transcriptional barrier. Loss of m6A leads to aberrantly elongated chimeric mRNAs due to impaired transcriptional termination. Overall, the results highlight a regulatory mechanism coupling m6A metabolism to cleavage and polyadenylation processes, serving as a guardian against aberrant transcriptional read-throughs.
Article
Biochemistry & Molecular Biology
Jean-Marie Bourhis, Filip Yabukarski, Guillaume Communie, Robert Schneider, Valentina A. Volchkova, Mickael Freneat, Francine C. Gerard, Corinne Ducournau, Caroline Mas, Nicolas Tarbouriech, Malene Ringkjobing Jensen, Viktor E. Volchkov, Martin Blackledge, Marc Jamin
Summary: The study investigated the interactions between the phosphoprotein (P) and the nucleoprotein (N) in the Paramyxoviridae's transcription/replication complex. The structural properties of the C-terminal X domain (P-XD) of Nipah (NiV) and Hendra virus (HeV) P protein were characterized. The experiments demonstrated that NiV P-XD adopted different conformations in solution, formed dimers, and played a possible role in viral replication.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bowen Liu, Helena Chan, Elda Bauda, Carlos Contreras-Martel, Laure Bellard, Anne-Marie Villard, Caroline Mas, Emmanuelle Neumann, Daphna Fenel, Adrien Favier, Monica Serrano, Adriano O. Henriques, Christopher D. A. Rodrigues, Cecile Morlot
Summary: This study revealed that some components of specialized secretion systems in Gram-negative bacteria include ring-forming proteins, which may be promoted by RBMs domain. Meanwhile, the transport system SpoIIIA-SpoIIQ complex in Gram-positive bacteria during spore formation was also investigated for its assembly in the double membrane.
JOURNAL OF STRUCTURAL BIOLOGY
(2022)
Article
Biology
Matthew Jessop, Karine Huard, Ambroise Desfosses, Guillaume Tetreau, Diego Carriel, Maria Bacia-Verloop, Caroline Mas, Philippe Mas, Angelique Fraudeau, Jacques-Philippe Colletier, Irina Gutsche
Summary: Bacterial homologous lysine and arginine decarboxylases play important roles in acid stress response, physiology, antibiotic resistance, and virulence. In this study, the polymerisation behavior of the arginine decarboxylase from Providencia stuartii is investigated and compared with the lysine decarboxylase from Escherichia coli. The findings reveal significant differences in their assembly mechanisms and provide a basis for future exploration of supramolecular assembly in the superfamily of arginine and lysine decarboxylases.
COMMUNICATIONS BIOLOGY
(2022)
Article
Cell Biology
Christopher Swale, Valeria Bellini, Matthew W. Bowler, Nardella Flore, Marie-Pierre Brenier-Pinchart, Dominique Cannella, Lucid Belmudes, Caroline Mas, Yohann Coute, Fabrice Laurent, Artur Scherf, Alexandre Bougdour, Mohamed-Ali Hakimi
Summary: The Apicomplexa, a phylum of single-celled protozoa, cause severe parasitic diseases in humans and animals. Current therapeutics are limited by their efficacy and resistance. In this study, altiratinib, originally developed for glioblastoma, is identified as a potential drug candidate with broad spectrum activity against apicomplexans. Altiratinib specifically targets the TgPRP4K of T. gondii and inhibits the development of intracellular parasites. The molecular basis of the inhibitory mechanism and species selectivity is further elucidated.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Antonio Iorio, Celine Brochier-Armanet, Caroline Mas, Fabio Sterpone, Dominique Madern
Summary: This study unveils the intimate relationship between protein dynamics and allostery, and identifies key dynamic mutations in the evolution of allostery. These mutations induce drastic changes in the conformational landscape, allowing access to typical conformers of allosteric proteins. This research is of great importance for understanding the evolution of protein function.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Virology
Francine C. A. Gerard, Jean-Marie Bourhis, Caroline Mas, Anais Branchard, Duc Duy Vu, Sylvia Varhoshkova, Cedric Leyrat, Marc Jamin
Summary: This study reconstituted a soluble heterodimeric complex between the nucleoprotein and phosphoprotein of rabies virus and solved the crystal structure of the complex. The results showed that the chaperone module undergoes a disordered-order transition during assembly and that the chaperone module and RNA-mediated polymerization reduce the ability of the RNA binding cavity to open and close.
Article
Biophysics
Sylvie Saleun, Caroline Mas, Aline Le Roy, Magalie Penaud-Budloo, Oumeya Adjali, Veronique Blouin, Christine Ebel
Summary: Recombinant adeno-associated virus virus-derived vectors (rAAVs) are widely used in vivo gene therapies due to their safety profile. However, rAAV production often results in a heterogeneous vector population with undesired empty particles. Analytical ultracentrifugation sedimentation velocity (AUC-SV) is a gold standard technique to measure the relative amounts of each vector subpopulation and components. This letter discusses the principle and practice of using AUC for rAAVs characterization, including the use of interference optics to estimate weight percentages of different capsid populations and the genome size incorporated in rAAV particles.
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2023)