Article
Chemistry, Multidisciplinary
Dari Kimanius, Gustav Zickert, Takanori Nakane, Jonas Adler, Sebastian Lunz, Carola-Bibiane Schonlieb, Ozan Oktem, Sjors H. W. Scheres
Summary: This paper introduces a regularization framework for cryo-EM structure determination that utilizes prior knowledge about biological structures through a convolutional neural network trained on known macromolecular structures. The method yields better reconstructions than current state-of-the-art techniques for simulated data, and possibilities for extending this work to experimental cryo-EM data are discussed.
Article
Multidisciplinary Sciences
Xudong Wu, Tom A. Rapoport
Summary: The Legobody approach allows structure determination of small proteins using cryo-EM, by rigidly attaching a nanobody to two scaffolds for particle alignment. This method overcomes size limitations, demonstrated by obtaining high-resolution maps for the KDEL receptor and the RBD of SARS-CoV-2 spike protein.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Biochemistry & Molecular Biology
Koji Yonekura, Saori Maki-Yonekura, Kiyofumi Takaba
Summary: Three-dimensional electron diffraction (3D ED) is a technique used in transmission electron microscopy for determining atomic structures from small crystals. It can be applied to various targets such as proteins, polypeptides, and organic compounds, and utilizes AI control to process a large amount of data efficiently. Recent results include the determination of structures and pathogenic mechanisms of polypeptides associated with ALS, the discovery of the double helical structure of nanographene promoting nanofiber formation, and the characterization of structural properties of an organic semiconductor with disordered regions. The limitations and prospects of 3D ED compared to X-ray free electron lasers for microcrystallography are also discussed.
Article
Chemistry, Multidisciplinary
Carsten E. Seyfert, Christoph Porten, Biao Yuan, Selina Deckarm, Fabian Panter, Chantal D. Bader, Janetta Coetzee, Felix Deschner, Kamaleddin H. M. E. Tehrani, Paul G. Higgins, Harald Seifert, Thomas C. Marlovits, Jennifer Herrmann, Rolf Mueller
Summary: In recent decades, the pipeline for antibiotics targeting Gram-negative bacteria has become depleted due to the insufficiency in potency, pharmacokinetic properties, and toxicity of most discovered candidates. A new class of promising drug candidates called darobactins has been developed, which bind to a novel antibiotic target called BamA, an outer membrane protein. This study presents the cryo-EM structures of the Bam complex with darobactin 9 (D9) and the biotechnological generation of twenty new darobactins, including halogenated analogs, using an optimized purification method. The newly engineered darobactin 22 binds more effectively to BamA and exhibits 32-fold improved activity against clinically relevant pathogens such as carbapenem-resistant Acinetobacter baumannii, without any observed toxic effects.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biology
Ruben Sanchez-Garcia, Josue Gomez-Blanco, Ana Cuervo, Jose Maria Carazo, Carlos Oscar S. Sorzano, Javier Vargas
Summary: Sanchez-Garcia et al. introduce DeepEMhancer, a deep learning-based method for automatic post-processing of raw cryo-electron microscopy density maps. It globally improves local quality of density maps and shows potential as a useful tool for structures without readily available PDB models.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biology
Stefan T. Huber, Edin Sarajlic, Roeland Huijink, Felix Weis, Wiel H. Evers, Arjen J. Jakobi
Summary: Nanofluidic sample supports can be used to prepare cryo-EM specimens with reproducible ice thickness, solving the problem of sample preparation difficulty, aiding in the automation of workflows, and expanding the applications of cryo-EM.
Article
Multidisciplinary Sciences
Yanting Tang, An Mu, Yuying Zhang, Shan Zhou, Weiwei Wang, Yuezheng Lai, Xiaoting Zhou, Fengjiang Liu, Xiuna Yang, Hongri Gong, Quan Wang, Zihe Rao
Summary: Encapsulins containing dye-decolorizing peroxidase (DyP)-type peroxidases play a role in protecting prokaryotic cells against oxidative stress. Through isolating and studying a native cargo-packaging encapsulin from Mycobacterium smegmatis, researchers have determined the high-resolution structure and proposed a potential mechanism for hydrogen peroxide removal. The study suggests DyP as the primary cargo protein of mycobacterial encapsulins and a potential target for antituberculosis drug discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Xiulian Yu, Tao Ni, George Munson, Peijun Zhang, Robert J. C. Gilbert
Summary: In this study, the structure of Perforin-2 in different conformations was determined using multiple techniques. The mechanism of pore formation in acidification conditions was found to be related to the conformational transition of the pre-pores, and it was observed that PFN2 pores mainly exist as incomplete arc structures on membranes.
Article
Biochemical Research Methods
Jiahua He, Sheng-You Huang
Summary: Cryo-electron microscopy (cryo-EM) is an important method in structure determination, and the EMNUSS framework can accurately annotate the secondary structures of cryo-EM maps, demonstrating good accuracy and robustness across various resolutions.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Xiulian Yu, Tao Ni, George Munson, Peijun Zhang, Robert J. C. Gilbert
Summary: This study investigated the conformational transition of PFN2 from pre-pore to pore structures. The complete pre-pore rings found in isolation could convert into pores with different conformations. On membranes, however, the assembled PFN2 pre-pores showed various degrees of completeness, while the pores were mainly incomplete arc structures. It was also found that both assemblies utilized the P2 beta-hairpin for binding to the lipid membrane surface. These findings provide insights into the molecular mechanism of PFN2 in forming pores on targeted membranes.
Article
Chemistry, Physical
Holger Klein, Marion Bellavoine, Dimitri Znaj
Summary: Conventional X-ray diffraction is not effective in characterizing secondary phases in metallic samples, while electron diffraction provides better spatial resolution. This study demonstrates the successful determination of the structures of three different phases in Al-based alloys using three-dimensional electron diffraction tomography.
JOURNAL OF ALLOYS AND COMPOUNDS
(2022)
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
Biochemistry & Molecular Biology
Shintaroh Kubo, Shun Kai Yang, Corbin S. Black, Daniel Dai, Melissa Valente-Paterno, Jacek Gaertig, Muneyoshi Ichikawa, Khanh Huy Bui
Summary: Cilia are thin microtubule-based protrusions found in eukaryotic cells, responsible for propelling the movement of ciliated protists and sperm cells, as well as facilitating mucus flow in the trachea to protect the human body from viral infections. The main force generators of ciliary beating are the outer dynein arms (ODAs), which attach to the doublet microtubules and induce bending through conformational changes driven by ATP hydrolysis. The structure of the native ODA complex attached to the doublet microtubule has been revealed through cryo-electron microscopy, showing how the ODA complex is attached to the doublet microtubule via the docking complex in its native state, leading to remodeling and activation.
Article
Engineering, Electrical & Electronic
Harshit Gupta, Michael T. McCann, Laurene Donati, Michael Unser
Summary: CryoGAN is a new paradigm for single-particle cryo-electron microscopy reconstruction based on unsupervised deep adversarial learning, achieving 3D structure reconstruction via distribution matching and skipping pose estimation or marginalization. It has shown success in recovering correct structures in an idealized mathematical model and achieving 10.8 angstrom resolution on a realistic synthetic dataset.
IEEE TRANSACTIONS ON COMPUTATIONAL IMAGING
(2021)
Article
Biochemical Research Methods
Amanda A. Riccio, Jonathan Bouvette, Matthew J. Longley, Juno M. Krahn, Mario J. Borgnia, William C. Copeland
Summary: The mitochondrial replisome is crucial for replicating mtDNA, with Twinkle helicase being a key protein component. Studying SF4 helicases helps understand common themes like self-assembly, ATP-dependent translocation, and formation of protein complexes. The methods described can support future high-resolution studies of Twinkle helicase or other SF4 helicases.
Article
Chemistry, Multidisciplinary
Max T. B. Clabbers, Tim Gruene, Eric van Genderen, Jan Pieter Abrahams
ACTA CRYSTALLOGRAPHICA A-FOUNDATION AND ADVANCES
(2019)
Meeting Abstract
Biophysics
Cecilia Wallin, Yoshitaka Hiruma, Sebastian Warmlander, Isabelle Huvent, Juri Jarvet, Jan Pieter Abrahams, Astrid Graslund, Guy Lippens, Jinghui Luo
BIOPHYSICAL JOURNAL
(2019)
Article
Multidisciplinary Sciences
Mina Moradi, Nadia L. Opara, Ludovico G. Tulli, Christian Waeckerlin, Scott J. Dalgarno, Simon J. Teat, Milos Baljozovic, Olha Popova, Eric van Genderen, Armin Kleibert, Henning Stahlberg, Jan Pieter Abrahams, Celestino Padeste, Philippe F-X Corvini, Thomas A. Jung, Patrick Shahgaldian
Article
Chemistry, Multidisciplinary
Andrea D. Merg, Gavin Touponse, Eric van Genderen, Xiaobing Zuo, Alisina Bazrafshan, Thorsten Blum, Spencer Hughes, Khalid Salaita, Jan Pieter Abrahams, Vincent P. Conticello
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2019)
Article
Chemistry, Multidisciplinary
Tatiana Latychevskaia, Jan Pieter Abrahams
ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS
(2019)
Article
Chemistry, Multidisciplinary
Mauro Gemmi, Enrico Mugnaioli, Tatiana E. Gorelik, Ute Kolb, Lukas Palatinus, Philippe Boullay, Sven Hovmoller, Jan Pieter Abrahams
ACS CENTRAL SCIENCE
(2019)
Article
Multidisciplinary Sciences
Thorsten B. Blum, Sevasti Filippidou, Mathilda Fatton, Pilar Junier, Jan Pieter Abrahams
SCIENTIFIC REPORTS
(2019)
Article
Chemistry, Multidisciplinary
Andrea D. Merg, Eric van Genderen, Alisina Bazrafshan, Hanquan Su, Xiaobing Zuo, Gavin Touponse, Thorsten B. Blum, Khalid Salaita, Jan Pieter Abrahams, Vincent P. Conticello
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Multidisciplinary Sciences
Joachim M. Matz, Benjamin Drepper, Thorsten B. Blum, Eric van Genderen, Alana Burrell, Peer Martin, Thomas Stach, Lucy M. Collinson, Jan Pieter Abrahams, Kai Matuschewski, Michael J. Blackman
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Microscopy
J. Paul van Schayck, Eric van Genderen, Erik Maddox, Lucas Roussel, Hugo Boulanger, Erik Frojdh, Jan-Pieter Abrahams, Peter J. Peters, Raimond B. G. Ravelli
Article
Biotechnology & Applied Microbiology
Zhenzhen Zhang, Kai Wen, Chao Zhang, Fabrice Laroche, Zhenglong Wang, Qiang Zhou, Zunfeng Liu, Jan Pieter Abrahams, Xiang Zhou
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2020)
Article
Physics, Applied
Pooja Thakkar, Vitaliy A. Guzenko, Peng-Han Lu, Rafal E. Dunin-Borkowski, Jan Pieter Abrahams, Soichiro Tsujino
JOURNAL OF APPLIED PHYSICS
(2020)
Article
Biochemical Research Methods
Thorsten B. Blum, Dominique Housset, Max T. B. Clabbers, Eric van Genderen, Maria Bacia-Verloop, Ulrich Zander, Andrew A. McCarthy, Guy Schoehn, Wai Li Ling, Jan Pieter Abrahams
Summary: Electron diffraction in protein crystallography can be improved by limiting dynamical scattering through data collection from thin crystals and using low-noise detectors. Likelihood-based correction can further reduce the dynamical component in refinement, leading to improvements in structural refinement and providing valuable insights into protein function. These advancements enhance the value of macromolecular electron crystallography as a complementary technique in structural biology.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Xiansha Xiao, Joost Willemse, Patrick Voskamp, Xinmeng Li, Andrea E. Prota, Meindert Lamers, Navraj Pannu, Jan Pieter Abrahams, Gilles P. van Wezel
Summary: The study found that amino acid substitutions in the SsgB protein of Streptomyces bacteria led to ectopically placed septa and diagonally or longitudinally divided cells. This suggests that besides altering FtsZ, aa substitutions in SsgB also play a role in cell division regulation in Streptomyces.
Article
Chemistry, Multidisciplinary
Andrea D. Merg, Gavin Touponse, Eric van Genderen, Thorsten B. Blum, Xiaobing Zuo, Alisina Bazrafshan, Hew Ming Helen Siaw, Arthur McCanna, R. Brian Dyer, Khalid Salaita, Jan Pieter Abrahams, Vincent P. Conticello
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
