Article
Biochemistry & Molecular Biology
Sandra Schilbach, Shintaro Aibara, Christian Dienemann, Frauke Grabbe, Patrick Cramer
Summary: This study reveals the high-resolution structure of the transcription initiation complex and the mechanism of DNA opening, crucial for promoter-initiated transcription. TFIIE facilitates initiation by supporting the clamp head loop and regulating the TFIIH translocase.
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
Virology
Vijay S. Reddy, Xiaodi Yu, Michael A. Barry
Summary: This study reports the improved capsid structure of human adenovirus D26 (HAdV-D26), providing better understanding of protein-protein interactions in HAdV capsids and facilitating the efforts to modify and/or design adenoviral vectors with altered properties.
Article
Multidisciplinary Sciences
Xizi Chen, Xiaotong Yin, Jiabei Li, Zihan Wu, Yilun Qi, Xinxin Wang, Weida Liu, Yanhui Xu
Summary: This study investigates the mechanisms of TFIID and Mediator proteins in regulating transcription initiation and RNA polymerase activity, revealing their interactions and mutual regulation through structural analysis, as well as the phosphorylation process of Pol II CTD by CDK7.
Article
Multidisciplinary Sciences
Xizi Chen, Xinxin Wang, Weida Liu, Yulei Ren, Xuechun Qu, Jiabei Li, Xiaotong Yin, Yanhui Xu
Summary: RNA polymerase II-mediated eukaryotic transcription begins with the assembly of the preinitiation complex (PIC) on core promoters. The +1 nucleosome, positioned about 40 base pairs downstream of the transcription start site (TSS), acts as a barrier to transcription. The study shows that the PIC-Mediator prefers binding to the T40N nucleosome located at the 40 base pairs downstream of the TSS and contacts the T50N nucleosome, but not the T70N nucleosome. The nucleosome facilitates the organization of PIC-Mediator on the promoter and may contribute to transcription initiation. The study reveals the molecular mechanism of PIC-Mediator organization on chromatin and emphasizes the significance of the +1 nucleosome in regulating transcription initiation.
Article
Multidisciplinary Sciences
Liqiang Shen, Giorgio Lai, Linlin You, Jing Shi, Xiaoxian Wu, Maria Puiu, Zhanxi Gu, Yu Feng, Yulia Yuzenkova, Yu Zhang
Summary: This study presents the cryo-EM structures of cyanobacterial transcription initiation complexes, revealing the role of SI3-& sigma; arch interaction in transcription initiation of cyanobacteria. Disruption of this structure affects the growth and stress response of cyanobacteria.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Linda Warfield, Rafal Donczew, Lakshmi Mahendrawada, Steven Hahn
Summary: This study investigates the genome-wide roles of the mediator factor (MED) in transcription. Rapid depletion of the activator-binding domain (Tail) of MED reveals that it only regulates a small subset of genes. The study also classifies genes into tail-dependent and tail-independent categories and discusses their implications for MED, other coactivators, and transcriptional regulation mechanisms.
Article
Biochemistry & Molecular Biology
Jie Wang, Long-Jiang Yu, Wenda Wang, Qiujing Yan, Tingyun Kuang, Xiaochun Qin, Jian-Ren Shen
Summary: Photosystem I (PSI), a crucial component in photosynthesis, has been structurally analyzed in complex with light-harvesting complex I (LHCI) to reveal the arrangement of proteins, cofactors, and newly identified lipid molecules. The research sheds light on the mechanisms of light-energy harvesting, transfer, and supercomplex assembly.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2021)
Article
Cell Biology
Kevin M. Andre, Nathalie Giordanengo Aiach, Veronica Martinez-Fernandez, Leo Zeitler, Adriana Alberti, Arach Goldar, Michel Werner, Cyril Denby Wilkes, Julie Soutourina
Summary: Chromatin organization is crucial for transcriptional regulation. Mediator and RSC contribute to chromatin remodeling and transcriptional regulation by establishing physical contact and coordinating their functions.
Article
Biochemistry & Molecular Biology
Yan Qin, Yuqiao Zhou, Yinghua Cao, Yanpeng Ren, Pujuan Deng, Junyi Jiang, Zhanxin Wang
Summary: The multicomponent PAF1C is an important transcription elongation factor that regulates genome-wide transcription. In this study, the structural core of the yeast PAF1C was evaluated, and the interaction details among its components were observed. A new binding surface of Rtf1 on PAF1C was identified, and the C-terminal sequence of Rtf1 was found to have changed during evolution. This work provides a precise model of PAF1C and enhances our understanding of its molecular mechanism and in vivo function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Vivian Cody, Jia Q. Truong, Bruce A. Holdsworth, Jessica K. Holien, Samantha J. Richardson, David K. Chalmers, David J. Craik
Summary: Human transthyretin (hTTR) amyloid deposits can disrupt cellular function, but the molecule VCP-6 can bind to and stabilize hTTR, reducing amyloid formation.
Review
Biochemistry & Molecular Biology
Srinivasan Rengachari, Sandra Schilbach, Patrick Cramer
Summary: Recent advancements in cryo-electron microscopy have allowed for the determination of multiple structures of Mediator bound to the RNA polymerase II transcription initiation machinery. As a result, we now have comprehensive structures of both yeast and human Mediator complexes and a better understanding of their interactions with the Pol II pre-initiation complex. In this review, we summarize recent achievements and discuss their implications for future studies on Mediator and its role in gene regulation.
BIOLOGICAL CHEMISTRY
(2023)
Article
Biology
Yuanyuan Shi, Jian Chen, Wei-Jie Zeng, Miao Li, Wenxue Zhao, Xing-Ding Zhang, Jie Yao
Summary: The study found that the Mediator complex subunit Med15 forms nuclear condensates through a novel mechanism. These condensates were sensitive to 1, 6-Hexanediol and showed rapid recovery after photobleaching. Overexpressing DYRK3 disrupted Med1 foci and Med15 foci, indicating a role in transcription coactivator condensate assembly.
Article
Biology
Alexander R. Leydon, Wei Wang, Hardik P. Gala, Sabrina Gilmour, Samuel Juarez-Solis, Mollye L. Zahler, Joseph E. Zemke, Ning Zheng, Jennifer L. Nemhauser
Summary: The plant corepressor TOPLESS (TPL) interacts with Mediator proteins to fully repress transcription, while multimer formation has minimal influence on TPL's repression strength.
Review
Biochemistry & Molecular Biology
Leonid A. Ilchuk, Marina V. Kubekina, Yulia D. Okulova, Yulia Yu. Silaeva, Victor V. Tatarskiy, Maxim A. Filatov, Alexandra V. Bruter
Summary: The Mediator complex is a multi-subunit protein complex that regulates eukaryotic gene transcription by facilitating the interaction between transcriptional factors and RNA polymerase II. While most studies focus on simple models like tumor cell lines and yeast, transgenic mouse models are necessary to explore the role of Mediator components in physiological processes, disease, and development. Due to the embryonic lethality of constitutive knockout models, conditional knockout models and corresponding activator strains are required. Recent developments in genetic engineering techniques have made these models more accessible. This review discusses existing mouse models for studying the Mediator and the data obtained from corresponding experiments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Diana Mendes Freire, Claude Gutierrez, Acely Garza-Garcia, Anna D. Grabowska, Ambre J. Sala, Kanchiyaphat Ariyachaokun, Terezie Panikova, Katherine S. H. Beckham, Andre Colom, Vivian Pogenberg, Michele Cianci, Anne Tuukkanen, Yves-Marie Boudehen, Antonio Peixoto, Laure Botella, Dmitri Svergun, Dirk Schnappinger, Thomas R. Schneider, Pierre Genevaux, Luiz Pedro Sorio de Carvalho, Matthias Wilmanns, Annabel H. A. Parret, Olivier Neyrolles
Article
Instruments & Instrumentation
Marcus Oscarsson, Antonia Beteva, David Flot, Elspeth Gordon, Matias Guijarro, Gordon Leonard, Sean McSweeney, Stephanie Monaco, Christoph Mueller-Dieckmann, Max Nanao, Didier Nurizzo, Alexander N. Popov, David von Stetten, Olof Svensson, Vicente Rey-Bakaikoa, Idrissou Chado, Leonard M. G. Chavas, Laurent Gadea, Patrick Gourhant, Tatiana Isabet, Pierre Legrand, Martin Savko, Serena Sirigu, William Shepard, Andrew Thompson, Uwe Mueller, Jie Nan, Mikel Eguiraun, Fredrick Bolmsten, Alberto Nardella, Antonio Milan-Otero, Marjolein Thunnissen, Michael Hellmig, Alexandra Kastner, Lukas Schmuckermaier, Martin Gerlach, Christian Feiler, Manfred S. Weiss, Matthew W. Bowler, Alexandre Gobbo, Gergely Papp, Jeremy Sinoir, Andrew A. McCarthy, Ivars Karpics, Marina Nikolova, Gleb Bourenkov, Thomas Schneider, Jordi Andreu, Guifre Cuni, Judith Juanhuix, Roeland Boer, Rasmus Fogh, Peter Keller, Claus Flensburg, Wlodek Paciorek, Clemens Vonrhein, Gerard Bricogne, Daniele de Sanctis
JOURNAL OF SYNCHROTRON RADIATION
(2019)
Article
Instruments & Instrumentation
Alexander Barannikov, Maxim Polikarpov, Petr Ershov, Vladimir Bessonov, Ksenia Abrashitova, Irina Snigireva, Vyacheslav Yunkin, Gleb Bourenkov, Thomas Schneider, Andrey A. Fedyanin, Anatoly Snigirev
JOURNAL OF SYNCHROTRON RADIATION
(2019)
Article
Biochemical Research Methods
Pedram Mehrabi, Eike C. Schulz, Michael Agthe, Sam Horrell, Gleb Bourenkov, David von Stetten, Jan-Philipp Leimkohl, Hendrik Schikora, Thomas R. Schneider, Arwen R. Pearson, Friedjof Tellkamp, R. J. Dwayne Miller
Article
Biochemical Research Methods
Maxim Polikarpov, Gleb Bourenkov, Irina Snigireva, Anatoly Snigirev, Sophie Zimmermann, Krisztian Csanko, Sandor Brockhauser, Thomas R. Schneider
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2019)
Article
Multidisciplinary Sciences
Andrea Alfieri, Fabrizio G. Doccula, Riccardo Pederzoli, Matteo Grenzi, Maria Cristina Bonza, Laura Luoni, Alessia Candeo, Neli Romano Armada, Alberto Barbiroli, Gianluca Valentini, Thomas R. Schneider, Andrea Bassi, Martino Bolognesi, Marco Nardini, Alex Costa
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Viktor Ahlberg Gagner, Ida Lundholm, Maria-Jose Garcia-Bonete, Helena Rodilla, Ran Friedman, Vitali Zhaunerchyk, Gleb Bourenkov, Thomas Schneider, Jan Stake, Gergely Katona
SCIENTIFIC REPORTS
(2019)
Article
Biochemistry & Molecular Biology
Masahiro Nishimura, Yasuhiro Arimura, Kayo Nozawa, Hitoshi Kurumizaka
JOURNAL OF BIOCHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Azadeh Shahsavar, Peter Stohler, Gleb Bourenkov, Iwan Zimmermann, Martin Siegrist, Wolfgang Guba, Emmanuel Pinard, Steffen Sinning, Markus A. Seeger, Thomas R. Schneider, Roger J. P. Dawson, Poul Nissen
Summary: This study utilized synthetic single-domain antibodies and serial synchrotron crystallography to determine the structure of GlyT1 in complex with an inhibitor, revealing that the inhibitor locks GlyT1 in an inward-open conformation and binds at the intracellular gate of the release pathway. These findings define the mechanism of inhibition and provide insights for the rational design of new, clinically efficacious GlyT1 inhibitors.
Article
Multidisciplinary Sciences
Sebastian Guenther, Patrick Y. A. Reinke, Yaiza Fernandez-Garcia, Julia Lieske, Thomas J. Lane, Helen M. Ginn, Faisal H. M. Koua, Christiane Ehrt, Wiebke Ewert, Dominik Oberthuer, Oleksandr Yefanov, Susanne Meier, Kristina Lorenzen, Boris Krichel, Janine-Denise Kopicki, Luca Gelisio, Wolfgang Brehm, Ilona Dunkel, Brandon Seychell, Henry Gieseler, Brenna Norton-Baker, Beatriz Escudero-Perez, Martin Domaracky, Sofiane Saouane, Alexandra Tolstikova, Thomas A. White, Anna Haenle, Michael Groessler, Holger Fleckenstein, Fabian Trost, Marina Galchenkova, Yaroslav Gevorkov, Chufeng Li, Salah Awel, Ariana Peck, Miriam Barthelmess, Frank Schluenzen, P. Lourdu Xavier, Nadine Werner, Hina Andaleeb, Najeeb Ullah, Sven Falke, Vasundara Srinivasan, Bruno Alves Franca, Martin Schwinzer, Hevila Brognaro, Cromarte Rogers, Diogo Melo, Joanna J. Zaitseva-Doyle, Juraj Knoska, Gisel E. Pena-Murillo, Aida Rahmani Mashhour, Vincent Hennicke, Pontus Fischer, Johanna Hakanpaa, Jan Meyer, Philip Gribbon, Bernhard Ellinger, Maria Kuzikov, Markus Wolf, Andrea R. Beccari, Gleb Bourenkov, David von Stetten, Guillaume Pompidor, Isabel Bento, Saravanan Panneerselvam, Ivars Karpics, Thomas R. Schneider, Maria Marta Garcia-Alai, Stephan Niebling, Christian Guenther, Christina Schmidt, Robin Schubert, Huijong Han, Juliane Boger, Diana C. F. Monteiro, Linlin Zhang, Xinyuanyuan Sun, Jonathan Pletzer-Zelgert, Jan Wollenhaupt, Christian G. Feiler, Manfred S. Weiss, Eike-Christian Schulz, Pedram Mehrabi, Katarina Karnicar, Aleksandra Usenik, Jure Loboda, Henning Tidow, Ashwin Chari, Rolf Hilgenfeld, Charlotte Uetrecht, Russell Cox, Andrea Zaliani, Tobias Beck, Matthias Rarey, Stephan Guenther, Dusan Turk, Winfried Hinrichs, Henry N. Chapman, Arwen R. Pearson, Christian Betzel, Alke Meents
Summary: The study identified 37 compounds that bind to the SARS-CoV-2 main protease through a high-throughput x-ray crystallographic screen of two repurposing drug libraries. Among these compounds, one peptidomimetic and six nonpeptidic compounds showed antiviral activity in cell-based viral reduction assays at nontoxic concentrations. The identification of two allosteric binding sites presents potential targets for drug development against SARS-CoV-2.
Article
Multidisciplinary Sciences
Jacob M. Musser, Klaske J. Schippers, Michael Nickel, Giulia Mizzon, Andrea B. Kohn, Constantin Pape, Paolo Ronchi, Nikolaos Papadopoulos, Alexander J. Tarashansky, Jorg U. Hammel, Florian Wolf, Cong Liang, Ana Hernandez-Plaza, Carlos P. Cantalapiedra, Kaia Achim, Nicole L. Schieber, Leslie Pan, Fabian Ruperti, Warren R. Francis, Sergio Vargas, Svenja Kling, Maike Renkert, Maxim Polikarpov, Gleb Bourenkov, Roberto Feuda, Imre Gaspar, Pawel Burkhardt, Bo Wang, Peer Bork, Martin Beck, Thomas R. Schneider, Anna Kreshuk, Gert Worheide, Jaime Huerta-Cepas, Yannick Schwab, Leonid L. Moroz, Detlev Arendt
Summary: Through whole-body single-cell RNA sequencing in sponges, researchers identified 18 distinct cell types, including contractile pinacocytes, amoeboid phagocytes, and secretory neuroid cells. These cells interact closely with digestive choanocytes, which express scaffolding and receptor proteins, indicating a communication system organized around sponge digestive chambers. Visualizing neuroid cells revealed secretory vesicles and cellular projections enwrapping choanocyte microvilli and cilia, suggesting the presence of conserved modules that may have evolved into synaptic structures in other animals' nervous systems.
Article
Chemistry, Physical
Soeren Rindfleisch, Matthias Krull, Jon Uranga, Tobias Schmidt, Fabian Rabe von Pappenheim, Laura Liliana Kirck, Angeliki Balouri, Thomas Schneider, Ashwin Chari, Ronald Kluger, Gleb Bourenkov, Ulf Diederichsen, Ricardo A. Mata, Kai Tittmann
Summary: This study presents crystallographic snapshots of human OMPDC in complex with substrate, analogues, transition-state analogues, and products, revealing that substrate carboxylate is protonated and forms a favorable low-barrier hydrogen bond with a negatively charged residue. The catalytic prowess of OMPDC primarily results from the transition-state stabilization by electrostatic interactions of the enzyme with charges spread over the substrate. These findings have relevance for the design of (de)carboxylase catalysts.
Article
Multidisciplinary Sciences
Kayo Nozawa, Yoshimasa Takizawa, Leonidas Pierrakeas, Chizuru Sogawa-Fujiwara, Kazumi Saikusa, Satoko Akashi, Ed Luk, Hitoshi Kurumizaka
Summary: The canonical nucleosome is the major packaging unit of eukaryotic chromatin, and the H3-H4 octasome is a nucleosome-like particle with alternative histone stoichiometry. The structure of the H3-H4 octasome is flexible.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Masahiro Nishimura, Yoshimasa Takizawa, Kayo Nozawa, Hitoshi Kurumizaka
Summary: The study reveals the structure of p53 binding to a nucleosome, providing valuable insights into the mechanism by which p53 binds to its target DNA and changes the chromatin structure for gene activation.
Meeting Abstract
Chemistry, Multidisciplinary
Thomas R. Schneider
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2019)