Article
Biochemistry & Molecular Biology
Xiyu Dong, Lili K. Doerfel, Kai Sheng, Jessica N. Rabuck-Gibbons, Anna M. Popova, Dmitry Lyumkis, James R. Williamson
Summary: We investigated the assembly principles of 50S ribosomal subunits using cryo-EM and found that they assemble based on cooperative assembly blocks and defined dependencies. We resolved 13 intermediate structures that accumulate during synthesis, revealing the smallest known assembly core. Our findings shed light on the parallel pathways involved in the early and late assembly stages of the 50S subunit.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Amal Seffouh, Chirstian Trahan, Tanzila Wasi, Nikhil Jain, Kaustuv Basu, Robert A. Britton, Marlene Oeffinger, Joaquin Ortega
Summary: The protein RbgA is crucial for the folding of functional sites in the 50S subunit, with its binding regulating the maturation order of the sites in the presence of uL6.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Cangsong Shen, Chunyou Mao, Chanjuan Xu, Nan Jin, Huibing Zhang, Dan-Dan Shen, Qingya Shen, Xiaomei Wang, Tingjun Hou, Zhong Chen, Philippe Rondard, Jean-Philippe Pin, Yan Zhang, Jianfeng Liu
Summary: This study reveals the structure of a class-C heterodimeric GABA(B) receptor in its active form complexed with Gi1 protein, showing a unique binding mode of G protein interaction compared to other classes of GPCR. The active form of the transmembrane domain of this GABA(B) receptor differs from that of other GPCRs, leading to distinctive inter- and intra-subunit changes linked to agonist binding and G-protein activation in this heterodimeric complex.
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
Multidisciplinary Sciences
Joseph S. Snowden, Jehad Alzahrani, Lee Sherry, Martin Stacey, David J. Rowlands, Neil A. Ranson, Nicola J. Stonehouse
Summary: This study reanalyzed the structure of type I fatty acid synthases (FASs) and identified several differences in both structural and enzymatic domains between P. pastoris FAS and the prototypical yeast FAS from S. cerevisiae. By using focussed classification, the researchers were able to resolve and model the mobile acyl-carrier protein (ACP) domain, which is crucial for the function of FAS. The structure reported in this study will serve as a valuable resource for further engineering efforts to synthesize alternate products using yeast FAS.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Kashish Singh, Georg Bunzel, Benjamin Graf, Ka Man Yip, Meina Neumann-Schaal, Holger Stark, Ashwin Chari
Summary: Fatty acids play important metabolic roles in cells, and a study on yeast fatty acid synthesis reveals the enzymatic reactions and structures involved in this process. The acyl carrier protein (ACP) is crucial in the catalytic cycle of yeast fatty acid synthesis, shuttling substances between active sites. The structure of S. cerevisiae FAS is resolved, providing insights into cofactors and water networks involved in their recognition. This study also shows the potential of incorporating exogenous proteins to modulate fatty acid product profiles.
Article
Biochemistry & Molecular Biology
Jingdong Cheng, Giuseppe La Venuta, Benjamin Lau, Otto Berninghausen, Roland Beckmann, Ed Hurt
Summary: This study reveals important steps in the biogenesis of eukaryotic small subunits, including the release of U3 and the folding of RNA. These processes are essential for the formation of active 40S subunits.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Multidisciplinary Sciences
Yoko Fujita-Fujiharu, Yukihiko Sugita, Yuki Takamatsu, Kazuya Houri, Manabu Igarashi, Yukiko Muramoto, Masahiro Nakano, Yugo Tsunoda, Ichiro Taniguchi, Stephan Becker, Takeshi Noda
Summary: This study determines the structure of the Marburg virus nucleoprotein-RNA complex and provides mechanistic insight into the helical assembly of the nucleocapsid.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Anas Khawaja, Miriam Cipullo, Annika Krueger, Joanna Rorbach
Summary: This review summarizes the biogenesis of mitochondrial ribosomal subunits, mtSSU and mtLSU, based on structural findings, and discusses potential crosstalk between mtSSU and mtLSU assembly pathways as well as coordination between mitoribosome biogenesis and other processes involved in mitochondrial gene expression.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Junso Fujita, Fumiaki Makino, Haruyasu Asahara, Maiko Moriguchi, Shota Kumano, Itsuki Anzai, Jun-ichi Kishikawa, Yoshiharu Matsuura, Takayuki Kato, Keiichi Namba, Tsuyoshi Inoue
Summary: Functionalization of graphene is a crucial technology in various fields. We have developed an oxidative modification method using photoactivated ClO2 as a mild oxidant, which allows the graphene to retain its functionality for at least three months. By chemically functionalizing the graphene, we created an epoxidized graphene grid (EG-grid), which greatly improves the density and orientation distribution of protein particles for cryoEM analysis. The EG-grid enables atomic-resolution imaging and highly efficient high-resolution cryoEM structural analysis of biological macromolecules.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Jung-Hoon Lee, Daniel Bollschweiler, Tillman Schaefer, Robert Huber
Summary: This research provides insight into the structural plasticity of the HDAC complex and its functional mechanism in chromatin modification. The study reveals the composition of the yeast class II HDAC ensembles and their impact on transcriptional repression, highlighting the importance of HDAC subunits and nucleosome binding modules in regulating HDAC catalysis.
Article
Multidisciplinary Sciences
Bo Qin, Simon M. M. Lauer, Annika Balke, Carlos H. H. Vieira-Vieira, Jorg Buerger, Thorsten Mielke, Matthias Selbach, Patrick Scheerer, Christian M. T. Spahn, Rainer Nikolay
Summary: Ribosome biogenesis is a multi-step cellular process that involves the production, processing, folding, and modification of ribosomal RNAs (rRNAs) and ribosomal proteins. By using a minimal in vitro reconstitution system, researchers studied the early assembly phase of the bacterial 50S subunit and found that it occurs in a domain-wise fashion, with late assembly proceeding incrementally. The study also showed that ribosomal proteins and folded rRNA helices induce or stabilize rRNA folds within adjacent regions, creating cooperativity.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Jingdong Cheng, Otto Berninghausen, Roland Beckmann
Summary: Assembly of the mitoribosome involves numerous assembly factors, with late transitions mainly involving rRNA domains IV and V. Structures of the human 39S late assembly intermediates reveal several assembly factors maintaining the immature conformations of 16S rRNA, and unexpected deacylated tRNA in the ribosomal E-site, suggesting a role in 39S assembly.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Qinggong Wang, Qiuyuan Lu, Qiong Guo, Maikun Teng, Qingguo Gong, Xu Li, Yang Du, Zheng Liu, Yuyong Tao
Summary: This study presents the cryo-EM structures of the MT1-G(i) signaling complex and the MT2-G(i) signaling complex, which reveal distinctive features and potential drug targets for designing subtype-selective melatonergic drugs.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Kaihua Zhang, David Julius, Yifan Cheng
Summary: This study utilized cryo-EM to visualize conformational transitions of TRPV1, revealing the dynamic transitions of its selectivity filter in response to algogenic agents. The findings also demonstrate a general framework for understanding how TRP channels function as polymodal signal integrators.
Article
Biochemistry & Molecular Biology
Rainer Nikolay, Tarek Hilal, Sabine Schmidt, Bo Qin, David Schwefel, Carlos H. Vieira-Vieira, Thorsten Mielke, Joerg Buerger, Justus Loerke, Kazuaki Amikura, Timo Fluegel, Takuya Ueda, Matthias Selbach, Elke Deuerling, Christian M. T. Spahn
Summary: Ribosome biogenesis is a complex cellular process regulated by multiple factors, with study of prokaryotic ribosome biogenesis revealing insights into the maturation process of ribosomal subunits.
Article
Cell Biology
Nicolas A. Heyder, Gunnar Kleinau, David Speck, Andrea Schmidt, Sarah Paisdzior, Michal Szczepek, Brian Bauer, Anja Koch, Monique Gallandi, Dennis Kwiatkowski, Joerg Buerger, Thorsten Mielke, Annette G. Beck-Sickinger, Peter W. Hildebrand, Christian M. T. Spahn, Daniel Hilger, Magdalena Schacherl, Heike Biebermann, Tarek Hilal, Peter Kuehnen, Brian K. Kobilka, Patrick Scheerer
Summary: The study analyzed the structure of melanocortin-4 receptor and revealed the mechanism of agonist-induced receptor activation, as well as discussed the interactions between two anti-obesity drugs and the receptor.
Article
Biochemical Research Methods
Nicole Dimos, Carl P. O. Helmer, Andrea M. Chanique, Markus C. Wahl, Robert Kourist, Tarek Hilal, Bernhard Loll
Summary: Enzyme catalysis is a crucial technology for developing efficient and sustainable processes. Plants provide diverse enzymes that facilitate complex reactions. Cryo-electron microscopy can reveal the structures of plant enzymes, providing a pathway for developing new biocatalysts.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Alexandra Bergfort, Marco Preussner, Benno Kuropka, Ibrahim Avsar Ilik, Tarek Hilal, Gert Weber, Christian Freund, Tugce Aktas, Florian Heyd, Markus C. Wahl
Summary: The intrinsically unstructured protein C9ORF78 interacts tightly with the spliceosome remodeling factor BRR2, and its knockout leads to changes in splice site usage and exon skipping, dependent on BRR2.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Tarek Hilal, Benjamin Y. Killam, Milica Grozdanovic, Malgorzata Dobosz-Bartoszek, Justus Loerke, Joerg Buerger, Thorsten Mielke, Paul R. Copeland, Miljan Simonovic, Christian M. T. Spahn
Summary: This study investigated the mechanism of Sec UGA recoding in eukaryotes and found that it is different from the mechanism in bacteria. Cryo-electron microscopy was used to visualize a complex consisting of the noncoding Sec-insertion sequence (SECIS), SECIS-binding protein 2 (SBP2), and the 40S ribosomal subunit, which enables the Sec-specific elongation factor eEFSec to deliver Sec. Additionally, the ribosomal protein eS31 plays a role in connecting the Sec-specific transfer RNA (tRNASec) and SBP2.
Article
Chemistry, Multidisciplinary
Philip Nickl, Tarek Hilal, Daniel Olal, Ievgen Sergeevitch Donskyi, Jorg Radnik, Kai Ludwig, Rainer Haag
Summary: This study presents a method for preparing a graphene-based modified support film to address the problem of protein adsorption at the air-water interface in cryoEM. The chemical modification of graphene sheets allows for the covalent anchoring of unmodified proteins, which improves particle orientations and prevents protein denaturation. The application of the modified support film in single particle analysis demonstrates its potential for high resolution structure determination.
Article
Biochemistry & Molecular Biology
Vu Thuy Khanh Le-Trilling, Sofia Banchenko, Darius Paydar, Pia Madeleine Leipe, Lukas Binting, Simon Lauer, Andrea Graziadei, Robin Klingen, Christine Gotthold, Joerg Buerger, Thilo Bracht, Barbara Sitek, Robert Jan Lebbink, Anna Malyshkina, Thorsten Mielke, Juri Rappsilber, Christian M. T. Spahn, Sebastian Voigt, Mirko Trilling, David Schwefel
Summary: This study revealed that rat cytomegalovirus infection induces the loss of transcription factor STAT2, which is crucial for antiviral interferon signaling. It was found that viral protein E27 exploits the host-cell CRL4 complexes to degrade STAT2 through poly-ubiquitylation. Furthermore, structural analyses showed that E27 recruits STAT2 through a bipartite binding interface, partially overlapping with the IRF9 binding site.
Article
Multidisciplinary Sciences
Bo Qin, Simon M. M. Lauer, Annika Balke, Carlos H. H. Vieira-Vieira, Jorg Buerger, Thorsten Mielke, Matthias Selbach, Patrick Scheerer, Christian M. T. Spahn, Rainer Nikolay
Summary: Ribosome biogenesis is a multi-step cellular process that involves the production, processing, folding, and modification of ribosomal RNAs (rRNAs) and ribosomal proteins. By using a minimal in vitro reconstitution system, researchers studied the early assembly phase of the bacterial 50S subunit and found that it occurs in a domain-wise fashion, with late assembly proceeding incrementally. The study also showed that ribosomal proteins and folded rRNA helices induce or stabilize rRNA folds within adjacent regions, creating cooperativity.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Junqiao Jia, Tarek Hilal, Katherine E. Bohnsack, Aleksandar Chernev, Ning Tsao, Juliane Bethmann, Aruna Arumugam, Lane Parmely, Nicole Holton, Bernhard Loll, Nima Mosammaparast, Markus T. Bohnsack, Henning Urlaub, Markus C. Wahl
Summary: The study reveals that ASCC3, with the assistance of TRIP4 protein, can unwind DNA by threading one strand of the substrate duplex through both helicase units.
NATURE COMMUNICATIONS
(2023)
Editorial Material
Genetics & Heredity
Olivier Duss, Rainer Nikolay, Matthew L. Kraushar
Summary: The ribosome is an ancient macromolecular complex responsible for decoding mRNA and synthesizing proteins. A recent study by Holm et al. reveals evolutionary distinctions in the structure and kinetics of mRNA decoding by the human ribosome.
TRENDS IN GENETICS
(2023)
