Article
Biochemistry & Molecular Biology
Jose J. Gorbea Colon, Leon Palao III, Shin-Fu Chen, Hee Jong Kim, Laura Snyder, Yi-Wei Chang, Kuang-Lei Tsai, Kenji Murakami
Summary: Most eukaryotic promoter regions are divergently transcribed, but it is unclear how this occurs. A study using cryoelectron microscopy analyzed the assembly of the Saccharomyces cerevisiae Mediator complex with a PIC on a divergent promoter. The study found that a Med-PIC dimer is formed through the Mediator tail module induced by a homodimeric activator protein, allowing for opposite-directional transcription.
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
Biochemistry & Molecular Biology
Saurabh Sharma, Ramesh Kumar, Ayushi Jain, Manoj Kumar, Rahul Gauttam, Rajdeep Banerjee, Jayanta Mukhopadhyay, Jaya Sivaswami Tyagi
Summary: The DevR/DosR response regulator is involved in virulence, dormancy adaptation, and antibiotic tolerance mechanisms of Mycobacterium tuberculosis by regulating the expression of dormancy regulon genes. The study developed an in vivo transcription system specific to M. tuberculosis to investigate the interaction between DevR and RNA polymerase, providing insights into potential strategies to target DevR function. Additionally, the system proved useful for screening anti-DevR compounds.
BIOCHEMICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Anne M. Jecrois, M. Michael Dcona, Xiaoyan Deng, Dipankar Bandyopadhyay, Steven R. Grossman, Celia A. Schiffer, William E. Royer
Summary: C-terminal binding proteins 1 and 2 (CtBP1 and CtBP2) are transcriptional regulators that can activate or repress genes involved in cellular development, apoptosis, and metastasis. This study reveals the mechanism by which NADH triggers the tetramer formation of CtBP2 and demonstrates that the tetramer is the functional oligomeric form of CtBP2.
Article
Multidisciplinary Sciences
Radhika Malik, Robert E. Johnson, Louise Prakash, Satya Prakash, Iban Ubarretxena-Belandia, Aneel K. Aggarwal
Summary: The study investigates the structure of the DNA-Pol zeta complex and its ability to extend DNA synthesis past mismatched base pairs. The results reveal the conformational changes in the Pol zeta active site and how it responds to mismatched DNA, allowing for the proper binding and extension of nucleotides. This study provides valuable insights into the regulation of DNA synthesis in eukaryotes.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Xinyun Cao, Hande Boyaci, James Chen, Yu Bao, Robert Landick, Elizabeth A. Campbell
Summary: Fidaxomicin is effective in treating Cdiff infections with minimal impact on gut commensals, and its activity is determined by a specific binding determinant in Cdiff RNA polymerase.
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
Multidisciplinary Sciences
Pietro Fontana, Ying Dong, Xiong Pi, Alexander B. Tong, Corey W. Hecksel, Longfei Wang, Tian-Min Fu, Carlos Bustamante, Hao Wu
Summary: This study determined the near-complete structure of the cytoplasmic ring of the nuclear pore complex (NPC) using cryo-electron microscopy and AlphaFold prediction. Molecular interactions and the binding modes of Nup358, the largest NPC subunit, were also predicted. The findings shed light on the formation and function of the NPC.
Article
Biochemistry & Molecular Biology
Wei Liu, Jiening Wang, Veronique Comte-Miserez, Mengyu Zhang, Xuejing Yu, Qingfeng Chen, Henning Jacob Jessen, Andreas Mayer, Shan Wu, Sheng Ye
Summary: The eukaryotic VTC complex functions as a polyphosphate polymerase, synthesizing polyP from ATP and translocating it across the vacuolar membrane to maintain cellular P-i homeostasis. The cryo-EM structure of the VTC complex reveals a heteropentameric architecture, with Vtc4, Vtc3, and Vtc1 subunits. The structure suggests a resting state conformation of the polyP-selective channel, with a latch-like helix of Vtc4 limiting the entrance and a strongly electropositive pathway for polyP synthesis and translocation.
Article
Multidisciplinary Sciences
Shyamal Mosalaganti, Agnieszka Obarska-Kosinska, Marc Siggel, Reiya Taniguchi, Beata Turonova, Christian E. Zimmerli, Katarzyna Buczak, Florian H. Schmidt, Erica Margiotta, Marie-Therese Mackmull, Wim J. H. Hagen, Gerhard Hummer, Jan Kosinski, Martin Beck
Summary: This study combines artificial intelligence-based structure prediction with in situ structural biology to reveal the structure and function of the human nuclear pore complex (NPC) scaffold. The findings demonstrate the importance of linker nucleoporins in establishing the higher-order structure of the scaffold and suggest that it widens the central pore rather than stabilizing the fusion of the inner and outer nuclear membranes.
Article
Biology
Natalia Petrenko, Kevin Struhl
Summary: Differences in the transcriptional initiation process exist among eukaryotic species, such as the dynamic bridge of Mediator and variations in TBP occupancy. TFIID interacts strongly at downstream regions of the initiation site in flies, contrasting with yeast and mammals. The Mediator subunit Med26 and Taf7 interact near the Pol II pause region, but only in subsets of genes.
Article
Cell Biology
Xinxin Wang, Yilun Qi, Zhenning Wang, Li Wang, Aixia Song, Bolin Tao, Jiabei Li, Dan Zhao, Hongwei Zhang, Qianwei Jin, Yi-Zhou Jiang, Fei Xavier Chen, Yanhui Xu, Xizi Chen
Summary: This study identified a novel protein, RPAP2, which plays an important regulatory role in transcription initiation and DNA replication. RPAP2 inhibits the assembly of the pre-initiation complex (PIC) by preventing the interaction between Pol II and TFIIF, thereby limiting the transcription initiation of genes. Loss of RPAP2 leads to the accumulation of TFIIF and Pol II at the promoter regions, affecting gene expression.
Article
Biochemistry & Molecular Biology
Gaurika Garg, Christian Dienemann, Lucas Farnung, Juliane Schwarz, Andreas Linden, Henning Urlaub, Patrick Cramer
Summary: We provide mechanistic insights into the three major steps of human co-transcriptional pre-mRNA capping based on six different cryo-EM structures. The human mRNA capping enzyme, RNGTT, first docks to the Pol II stalk to position its triphosphatase domain near the RNA exit site. The capping enzyme then moves onto the Pol II surface, and its guanylyltransferase receives the pre-mRNA 5'-diphosphate end.
Article
Biochemistry & Molecular Biology
Ramy Kazan, Gabrielle Bourgeois, Christine Lazennec-Schurdevin, Eric Larquet, Yves Mechulam, Pierre-Damien Coureux, Emmanuelle Schmitt
Summary: This study investigates the late steps of translation initiation in Pyrococcus abyssi and reveals that aIF5B bound to GTP accelerates subunit joining without GTP hydrolysis. Crystal structures and cryo-EM analysis demonstrate the cooperative role of archaeal 5B and 1A factors in promoting a conformation of the initiator tRNA favorable to subunit joining.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Immunology
Wen Zhang, ZhiFei Li, Yufan Sun, Peng Cui, Jianhua Liang, Qinghe Xing, Jing Wu, Yanhui Xu, Wenhong Zhang, Ying Zhang, Lin He, Ning Gao
Summary: In this study, the structure of the Mycobacterium tuberculosis ribosome-clarithromycin complex was solved using cryo-EM technique, providing insights into the binding mechanism and specificity of clarithromycin. The presence of a single methyl group in clarithromycin was found to enhance its potency.
EMERGING MICROBES & INFECTIONS
(2022)
Article
Biochemistry & Molecular Biology
Soung-Hun Roh, Moses Kasembeli, Jesus G. Galaz-Montoya, Mike Trnka, Wilson Chun-Yu Lau, Alma Burlingame, Wah Chiu, David J. Tweardy
JOURNAL OF BIOLOGICAL CHEMISTRY
(2016)
Article
Multidisciplinary Sciences
Adam G. Larson, Daniel Elnatan, Madeline M. Keenen, Michael J. Trnka, Jonathan B. J. Ohnston, Alma L. Burlingame, David A. Agard, Sy Redding, Geeta J. Narlikar
Article
Cell Biology
Coral Y. Zhou, Caitlin I. Stoddard, Jonathan B. Johnston, Michael J. Trnka, Ignacia Echeverria, Eugene Palovcak, Andrej Sali, Alma L. Burlingame, Yifan Cheng, Geeta J. Narlikar
Article
Biology
Nathan Gamarra, Stephanie L. Johnson, Michael J. Trnka, Alma L. Burlingame, Geeta Narlikar
Article
Microbiology
Arabinda Nayak, Dong Young Kim, Michael J. Trnka, Craig H. Kerr, Peter V. Lidsky, David J. Stanley, Brianna Monique Rivera, Kathy H. Li, Alma L. Burlingame, Eric Jan, Judith Frydman, John D. Gross, Raul Andino
CELL HOST & MICROBE
(2018)
Article
Multidisciplinary Sciences
James E. Longbotham, Cynthia M. Chio, Venkatasubramanian Dharmarajan, Michael J. Trnka, Idelisse Ortiz Torres, Devrishi Goswami, Karen Ruiz, Alma L. Burlingame, Patrick R. Griffin, Danica Galonic Fujimori
NATURE COMMUNICATIONS
(2019)
Article
Chemistry, Analytical
Claudio Iacobucci, Christine Piotrowski, Ruedi Aebersold, Bruno C. Amaral, Philip Andrews, Katja Bernfur, Christoph Borchers, Nicolas I. Brodie, James E. Bruce, Yong Cao, Stephane Chaignepain, Juan D. Chavez, Stephane Claverol, Juergen Cox, Trisha Davis, Gianluca Degliesposti, Meng-Qiu Dong, Nufar Edinger, Cecilia Emanuelsson, Marina Gay, Michael Goetze, Francisco Gomes-Neto, Fabio C. Gozzo, Craig Gutierrez, Caroline Haupt, Albert J. R. Heck, Franz Herzog, Lan Huang, Michael R. Hoopmann, Nir Kalisman, Oleg Klykov, Zdenek Kukacka, Fan Liu, Michael J. MacCoss, Karl Mechtler, Ravit Mesika, Robert L. Moritz, Nagarjuna Nagaraj, Victor Nesati, Ana G. C. Neves-Ferreira, Robert Ninnis, Petr Novak, Francis J. O'Reilly, Matthias Pelzing, Evgeniy Petrotchenko, Lolita Piersimoni, Manolo Plasencia, Tara Pukala, Kasper D. Rand, Juri Rappsilber, Dana Reichmann, Carolin Sailer, Chris P. Sarnowski, Richard A. Scheltema, Carla Schmidt, David C. Schriemer, Yi Shi, J. Mark Skehel, Moriya Slavin, Frank Sobott, Victor Solis-Mezarino, Heike Stephanowitz, Florian Stengel, Christian E. Stieger, Esben Trabjerg, Michael Trnka, Marta Vilaseca, Rosa Viner, Yufei Xiang, Sule Yilmaz, Alex Zelter, Daniel Ziemianowicz, Alexander Leitner, Andrea Sinz
ANALYTICAL CHEMISTRY
(2019)
Article
Multidisciplinary Sciences
S. Sanulli, M. J. Trnka, V. Dharmarajan, R. W. Tibble, B. D. Pascal, A. L. Burlingame, P. R. Griffin, J. D. Gross, G. J. Narlikar
Article
Multidisciplinary Sciences
Alexander von Appen, Dollie LaJoie, Isabel E. Johnson, Michael J. Trnka, Sarah M. Pick, Alma L. Burlingame, Katharine S. Ullman, Adam Frost
Article
Biochemical Research Methods
Yi Liu, Michael J. Trnka, Shenheng Guan, Doyoung Kwon, Do-Hyung Kim, J. -J. Chen, Peter A. Greer, A. L. Burlingame, Maria Almira Correia
MOLECULAR & CELLULAR PROTEOMICS
(2020)
Article
Biology
Philip T. McGilvray, S. Andrei Anghel, Arunkumar Sundaram, Frank Zhong, Michael J. Trnka, James R. Fuller, Hong Hu, Alma L. Burlingame, Robert J. Keenan
Article
Multidisciplinary Sciences
Pau Castel, Srisathiyanarayanan Dharmaiah, Matthew J. Sale, Simon Messing, Gabrielle Rizzuto, Antonio Cuevas-Navarro, Alice Cheng, Michael J. Trnka, Anatoly Urisman, Dominic Esposito, Dhirendra K. Simanshu, Frank McCormick
Summary: This study investigated the role of Sin1 as a RAS effector through biochemical and structural methods, revealing that the interaction between Sin1 and RAS is not necessary for the function of mTORC2.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Nicholas A. Sanchez, Lena M. Kallweit, Michael J. Trnka, Charles L. Clemmer, Bassem Al-Sady
Summary: The study reveals that the reading and writing activities of H3K9me are significantly enhanced in the heterodimer, with higher recognition of H3K9me2 and a striking increased turnover rate for nucleosomal substrates. Cross-linking Mass Spectrometry suggests that differences between the homodimers and the unique activity of the heterodimer may be encoded in altered ground state conformations.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Amanda Jack, Luke S. Ferro, Michael J. Trnka, Eddie Wehri, Amrut Nadgir, Xammy Nguyenla, Douglas Fox, Katelyn Costa, Sarah Stanley, Julia Schaletzky, Ahmet Yildiz
Summary: Research shows that the N protein of SARS-CoV-2 forms biomolecular condensates with viral genomic RNA, facilitating packaging of the RNA genome into viral particles. This process is influenced by interactions within the N protein, which can be disrupted by small molecules.
Article
Biochemical Research Methods
K. Ramki, G. Thiruppathi, Selva Kumar Ramasamy, P. Sundararaj, P. Sakthivel
Summary: A chromone-based ratiometric fluorescent probe L2 was developed for the selective detection of Hg(II) in a semiaqueous solution. The probe exhibited enhanced fluorescence in its aggregated state and even higher fluorescence when chelated with Hg(II). The probe demonstrated high sensitivity and specificity for Hg(II) detection and was successfully applied for imaging Hg(II) in a living model.
Article
Biochemical Research Methods
Qun Zhang, Rui Yang, Gang Liu, Shiyan Jiang, Jiarui Wang, Juqiang Lin, Tingyin Wang, Jing Wang, Zufang Huang
Summary: This research aims to develop a cost-effective and portable method for measuring creatinine levels using the enhanced Tyndall effect phenomenon. The method offers a promising solution for monitoring renal healthcare in resource-limited settings.