Article
Multidisciplinary Sciences
Romany Abskharon, Michael R. Sawaya, David R. Boyer, Qin Cao, Binh A. Nguyen, Duilio Cascio, David S. Eisenberg
Summary: In this study, the structure of RNA-bound tau protein fibrils was determined using cryo-EM. The findings demonstrate that RNA is necessary for the integrity of the fibrils and reveal a potential mechanism for the nucleating effects of RNA in neurodegenerative diseases. This research provides insight into the formation of protein aggregates in these diseases.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(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
Virology
Samantha R. Hartmann, Daniel J. Goetschius, Jiafen Hu, Joshua J. Graff, Carol M. Bator, Neil D. Christensen, Susan L. Hafenstein
Summary: HPV is a significant health burden and a leading cause of virus-induced cancers, but studies have been hindered by restricted tropism. Alternative methods such as VLPs have been developed to overcome this issue, but structural studies have been limited by heterogeneity, fragility, and stability. By studying MmuPV1, a framework for continuing biochemical, genetic, and biophysical research for papillomaviruses has been provided.
Article
Biochemistry & Molecular Biology
Jing Zheng, Wenyuan Chen, Hao Xiao, Fan Yang, Jingdong Song, Lingpeng Cheng, Hongrong Liu
Summary: This study resolved the asymmetric structure of the podophage GP4 and identified a new topology of the tail components. The podophage GP4 has three types of tail fibers, which may provide evolutionary advantages in terms of host range and infection efficiency.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Clinton K. Lau, Francis J. O'Reilly, Balaji Santhanam, Samuel E. Lacey, Juri Rappsilber, Andrew P. Carter
Summary: Dynactin is a complex that activates dynein for ultra-processive transport along microtubules. Its structure, formed by an actin-related filament, is defined by a flexible shoulder domain. By combining multiple cryo-EM datasets and precise masking strategies, the research overcame domain flexibility and obtained high-resolution maps of the Dynactin structure. The unique architecture of the shoulder securely positions subunits and reveals the molecular basis for cargo adaptor binding at the pointed end.
Article
Multidisciplinary Sciences
Jinhuan Chen, Yifan Wang, Cong Xu, Kaijian Chen, Qiaoyu Zhao, Shutian Wang, Yue Yin, Chao Peng, Zhanyu Ding, Yao Cong
Summary: Cryo-EM structures of the mammalian PA28 alpha beta-iCP immunoproteasome and free iCP, combined with cross-linking data, reveal the complex architecture and suggest a distinct immunoproteasome activation mechanism.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Lizelle Lubbe, Bryan Trevor Sewell, Jeremy D. Woodward, Edward D. Sturrock
Summary: This study presents the first cryo-EM structures of full-length, glycosylated, soluble sACE (sACE(S1211)), revealing both monomeric and dimeric forms of the enzyme. The structures provide insights into the intradomain hinging, cooperativity, and homodimerization mechanisms of sACE. The observation of open conformation has implications for the design of sACE modulators.
Article
Biology
Koji Kato, Naoyuki Miyazaki, Tasuku Hamaguchi, Yoshiki Nakajima, Fusamichi Akita, Koji Yonekura, Jian-Ren Shen
Summary: The study reveals the structure of Photosystem II in solution at 1.95 angstrom resolution using single-particle cryo-electron microscopy, with a visible PsbY subunit and reduced electron beam damage by lowering the dosage, providing valuable insights for determining damage-free cryo-EM structures.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
You Yu, Shibai Li, Zheng Ser, Huihui Kuang, Thane Than, Danying Guan, Xiaolan Zhao, Dinshaw J. Patel
Summary: In this study, the cryo-EM structure of DNA-bound Saccharomyces cerevisiae Smc5/6 complex was determined, revealing intricate interactions among core subunits and the mechanism of DNA binding. The Smc5/6 complex was found to form a clamp that encircles the DNA, with multiple subunits binding to DNA in a nonsequence-specific manner. These findings are significant for our understanding of the importance of SMC complexes in maintaining chromatin organization and function throughout the cell cycle.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Alastair T. Gardiner, Katerina Naydenova, Pablo Castro-Hartmann, Tu C. Nguyen-Phan, Christopher J. Russo, Kasim Sader, C. Neil Hunter, Richard J. Cogdell, Pu Qian
Summary: The study reports the structure of the LH2 complex from Marichromatium purpuratum with a resolution of 2.4 angstroms determined by cryogenic electron microscopy. It reveals a heptameric ring unique among all known LH2 structures, controlling the resonant coupling of the long-wavelength energy absorption band, and describes distinct carotenoids and energy transfer pathways within the complex. These details provide key insights into the assembly and oligomeric form of purple bacterial LH2 complexes that were previously inaccessible by any technique.
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
Xin Yong, Guowen Jia, Zhe Liu, Chunzhuang Zhou, Jiamin Yi, Li Chen, Lu Chen, Yuan Wang, Qingxiang Sun, Daniel D. Billadeau, Zhaoming Su, Da Jia
Summary: In this study, the structure of the Drosophila Mon1-Ccz1-RMC1 complex was determined using cryogenic-electron microscopy. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1, explaining the binding specificity of the complex. The assembly of RMC1 with Mon1-Ccz1 is required for cellular RAB7A activation, autophagic functions, and organismal development in zebrafish.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Michael J. Sheedlo, Clarissa L. Durie, Jeong Min Chung, Louise Chang, Jacquelyn Roberts, Michele Swanson, Dana Borden Lacy, Melanie D. Ohi
Summary: This passage discusses the relationship between Legionella pneumophila and Legionnaires' disease, as well as the structure of the Dot/Icm T4SS core complex determined by single particle cryo-EM. It identifies new proteins contributing to the core T4SS structure and defines two areas of symmetry mismatch.
Article
Biology
Marc Kschonsak, Christine C. Jao, Christopher P. Arthur, Alexis L. Rohou, Philippe Bergeron, Daniel F. Ortwine, Steven J. McKerrall, David H. Hackos, Lunbin Deng, Jun Chen, Tianbo Li, Peter S. Dragovich, Matthew Volgraf, Matthew R. Wright, Jian Payandeh, Claudio Ciferri, John C. Tellis
Summary: The Na(V)1.7 channel has been identified as a potential analgesic target, but current channel-blocking drugs lack selectivity among the nine Na(V) channel subtypes. A recent study using cryo-EM revealed a new binding mechanism of the inhibitor GDC-0310 to Na(V)1.7, and a novel hybrid inhibitor series was designed to bridge the binding pockets of aryl- and acylsulfonamide inhibitors. This study highlights the power of cryo-EM methods in drug target discovery and emphasizes the importance of the membrane bilayer in optimizing selective Na(V) channel modulators.
Article
Biochemistry & Molecular Biology
Chloe Du Truong, Theodore A. Craig, Gaofeng Cui, Maria Victoria Botuyan, Rachel A. Serkasevich, Ka-Yi Chan, Georges Mer, Po-Lin Chiu, Rajiv Kumar
Summary: The study revealed that apo Pol zeta exhibits enhanced flexibility compared to its DNA-bound state, with concerted motions associated with expansion of the Pol zeta DNA-binding channel upon DNA binding. Additionally, a lysine residue obstructing the DNA-binding channel in apo Pol zeta was identified, suggesting a gating mechanism.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Babatunde Ekundayo, Davide Torre, Bertrand Beckert, Sergey Nazarov, Alexander Myasnikov, Henning Stahlberg, Dongchun Ni
Summary: The CRISPR-guided caspase (Craspase) complex consists of Cas7-11, CRISPR RNA (crRNA), and TPR-CHAT protein. It shows potential as a tool for gene therapy and biomedical research, but its regulation is not well understood. In this study, cryoelectron microscopy was used to determine the structures of the Dm Craspase complex to understand its regulation mechanism. It was found that DmTPR-CHAT stabilizes crRNA-bound DmCas7-11 in a closed conformation through interactions mediated by DmTPR-CHAT N-terminal domain, DmCas7-11 insertion finger, and Cas11-like domain, resulting in reduced target RNA accessibility and cleavage.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Marc Emmenegger, Elena De Cecco, David Lamparter, Raphael P. B. Jacquat, Julien Riou, Dominik Menges, Tala Ballouz, Daniel Ebner, Matthias M. Schneider, Itzel Condado Morales, Berre Dogancay, Jingjing Guo, Anne Wiedmer, Julie Domange, Marigona Imeri, Rita Moos, Chryssa Zografou, Leyla Batkitar, Lidia Madrigal, Dezirae Schneider, Chiara Trevisan, Andres Gonzalez-Guerra, Alessandra Carrella, Irina L. Dubach, Catherine K. Xu, Georg Meisl, Vasilis Kosmoliaptsis, Tomas Malinauskas, Nicola Burgess-Brown, Ray Owens, Stephanie Hatch, Juthathip Mongkolsapaya, Gavin R. Screaton, Katharina Schubert, John D. Huck, Feimei Liu, Florence Pojer, Kelvin Lau, David Hacker, Elsbeth Probst-Mueller, Carlo Cervia, Jakob Nilsson, Onur Boyman, Lanja Saleh, Katharina Spanaus, Arnold von Eckardstein, Dominik J. Schaer, Nenad Ban, Ching-Ju Tsai, Jacopo Marino, Gebhard F. X. Schertler, Nadine Ebert, Volker Thiel, Jochen Gottschalk, Beat M. Frey, Regina R. Reimann, Simone Hornemann, Aaron M. Ring, Tuomas P. J. Knowles, Milo A. Puhan, Christian L. Althaus, Ioannis Xenarios, David I. Stuart, Adriano Aguzzi
Summary: Effective public health measures against SARS-CoV-2 require understanding population-level immune responses. Researchers developed a blood immunoassay called TRABI to assess IgG response against SARS-CoV-2 proteins. They used TRABI for continuous seromonitoring of hospital patients and blood donors in Zurich from December 2019 to December 2020. Their findings revealed a decline in antibodies, an increase in cumulative incidence, and no difference in long-term complications between symptomatic and asymptomatic infections.
Correction
Biology
Valerie Biou, Ricardo Jorge Diogo Adaixo, Mohamed Chami, Pierre-Damien Coureux, Benoist Laurent, Veronique Yvette Ntsogo Enguene, Gisele Cardoso de Amorim, Nadia Izadi-Pruneyre, Christian Malosse, Julia Chamot-Rooke, Henning Stahlberg, Philippe Delepelaire
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Thomas Gruhl, Tobias Weinert, Matthew J. Rodrigues, Christopher J. Milne, Giorgia Ortolani, Karol Nass, Eriko Nango, Saumik Sen, Philip J. M. Johnson, Claudio Cirelli, Antonia Furrer, Sandra Mous, Petr Skopintsev, Daniel James, Florian Dworkowski, Petra Bath, Demet Kekilli, Dmitry Ozerov, Rie Tanaka, Hannah Glover, Camila Bacellar, Steffen Brunle, Cecilia M. Casadei, Azeglio D. Diethelm, Dardan Gashi, Guillaume Gotthard, Ramon Guixa-Gonzalez, Yasumasa Joti, Victoria Kabanova, Gregor Knopp, Elena Lesca, Pikyee Ma, Isabelle Martiel, Jonas Muhle, Shigeki Owada, Filip Pamula, Daniel Sarabi, Oliver Tejero, Ching-Ju Tsai, Niranjan Varma, Anna Wach, Sebastien Boutet, Kensuke Tono, Przemyslaw Nogly, Xavier Deupi, So Iwata, Richard Neutze, Jorg Standfuss, Gebhard Schertler, Valerie Panneels
Summary: This article reveals the early stages of the vision process through ultrafast time-resolved crystallography experiments, providing the latest research on vertebrate vision and insights into the molecular mechanisms of agonist-mediated GPCR activation.
Article
Multidisciplinary Sciences
Pablo Gainza, Sarah Wehrle, Alexandra Van Hall-Beauvais, Anthony Marchand, Andreas Scheck, Zander Harteveld, Stephen Buckley, Dongchun Ni, Shuguang Tan, Freyr Sverrisson, Casper Goverde, Priscilla Turelli, Charlene Raclot, Alexandra Teslenko, Martin Pacesa, Stephane Rosset, Sandrine Georgeon, Jane Marsden, Aaron Petruzzella, Kefang Liu, Zepeng Xu, Yan Chai, Pu Han, George F. Gao, Elisa Oricchio, Beat Fierz, Didier Trono, Henning Stahlberg, Michael Bronstein, Bruno E. Correia
Summary: Physical interactions between proteins are crucial for biological processes. A geometric deep-learning framework is used to generate fingerprints on protein surfaces to describe the key aspects of molecular recognition. Using this approach, several de novo protein binders were designed and successfully bound to different protein targets.
Article
Multidisciplinary Sciences
Diane C. A. Barret, Dina Schuster, Matthew J. Rodrigues, Alexander Leitner, Paola Picotti, Gebhard F. X. Schertler, U. Benjamin Kaupp, Volodymyr M. Korkhov, Jacopo Marino
Summary: Calmodulin (CaM) regulates ion channels to control calcium entry into cells, and mutations affecting this interaction are linked to fatal diseases. The structural basis of CaM regulation is not well understood. In retinal photoreceptors, CaM binds to the CNGB subunit of CNG channels and modulates the channel's sensitivity to changes in ambient light. This study provides the structural characterization of CaM regulation of a CNG channel using cryo-electron microscopy and proteomics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Editorial Material
Biochemistry & Molecular Biology
Jonathan Markert, Karolin Luger, Hayun Lee, Haidai Hu, Nicholas M. I. Taylor, Javier Fernandez-Martinez, Michael Rout, Nathan Alder
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Magnus Bloch, Isha Raj, Tillmann Pape, Nicholas M. I. Taylor
Summary: This study presents the cryo-EM structures of MRP4 in different physiologically relevant states, revealing its unusually broad substrate specificity and providing insights into its transport mechanism.
Article
Multidisciplinary Sciences
Galina Limorenko, Meltem Tatli, Rajasekhar Kolla, Sergey Nazarov, Marie-Theres Weil, David C. Schondorf, Daniela Geist, Peter Reinhardt, Dagmar E. Ehrnhoefer, Henning Stahlberg, Laura Gasparini, Hilal A. Lashuel
Summary: The authors present a method to produce co-factor-free fibrils from all full-length Tau isoforms, which allows for the reconstitution of pathology resembling Tau fibrils and the screening of Tau aggregation-modifying compounds for targeted therapies and PET tracers.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Haidai Hu, Philipp F. Popp, Monica Santiveri, Aritz Roa-Eguiara, Yumeng Yan, Freddie J. O. Martin, Zheyi Liu, Navish Wadhwa, Yong Wang, Marc Erhardt, Nicholas M. I. Taylor
Summary: In this study, the structure of Vibrio PomAB was determined by cryo-electron microscopy, revealing sodium binding sites, and a mechanism for ion translocation and selectivity was proposed through functional experiments and molecular dynamics simulations. The involvement of a dynamic helical motif in PomA was suggested to regulate the distance between PomA subunit cytoplasmic domains, stator unit activation, and torque transmission. Overall, this study provides mechanistic insights into ion selectivity and rotor incorporation of the stator unit of the bacterial flagellum.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Dongchun Ni, Xuhang Lu, Henning Stahlberg, Babatunde Ekundayo
Summary: Short prokaryotic argonaute (pAgo) and toll/interleukin-1 receptor/resistance protein (TIR)-analog of PAZ (APAZ) form a heterodimeric SPARTA complex that provides immunity to its prokaryotic host through an abortive infection mechanism. Monomeric SPARTA senses foreign RNA/DNA duplexes to assemble an active tetramer resulting in cell death by NAD depletion via an unknown mechanism. Our findings provide detailed structural and mechanistic insights into activating a short argonaute defense system.
Meeting Abstract
Biochemistry & Molecular Biology
Alexandra Van Hall-Beauvais, Pablo Gainza, Sarah Wehrle, Andreas Scheck, Anthony Marchand, Zander Harteveld, Casper Goverde, Dongchun Ni, Tan Shuguang, Priscilla Turelli, Didier Trono, Henning Stahlberg, Geroge Gao, Michael Bronstein, Bruno Correia