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)
Review
Biochemistry & Molecular Biology
Bogdan Toader, Fred J. Sigworth, Roy R. Lederman
Summary: Cryo-electron microscopy imaging allows us to understand the shape change and energy landscape of macromolecules. Current computational methods can recover distinct conformations from single-particle samples, but dealing with complex forms of heterogeneity, such as continuous transitional states and flexible regions, remains a challenge.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
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
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
Biochemistry & Molecular Biology
Akiko Kamegawa, Shota Suzuki, Hiroshi Suzuki, Kouki Nishikawa, Nobutaka Numoto, Yoshinori Fujiyoshi
Summary: In this study, the structure of aquaporin-2 (AQP2) was analyzed using single-particle cryo-electron microscopy (cryo-EM) technique. The analysis revealed information about the cytoplasmic extension and continuous density inside the channel pore associated with AQP2. The findings indicate that single-particle cryo-EM can be used to study water channels in their native states and in complexes with chemical compounds.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jeison Mendez, Edgar Garduno, Jose Maria Carazo, Carlos Oscar S. Sorzano
Summary: An accurate assignment of orientations in single-particle analysis is crucial for high-quality 3D map production, yet the problem's complexity often leads to multiple local minima in optimized goal functions. Validation methods are therefore essential to confirm the angular assignment and improve the resolution of 3D maps. This study introduces a graph-signal-processing-based methodology that analyzes correlation landscapes to estimate the reliability of assigned orientations, allowing for the identification of low-reliability images that may negatively impact the final 3D reconstruction.
JOURNAL OF STRUCTURAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Yixin Xu, Shangyu Dang
Summary: Cryo-sample preparation is a critical step in obtaining high-resolution macromolecule structures using cryo-EM, but it is often affected by high uncertainty and low reproducibility. Developing new methods to enhance cryo-sample quality is therefore an important research topic.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biology
Ashok R. Nayak, Montserrat Samso
Summary: Activation and inactivation of intracellular Ca2+ channel are regulated by the binding of Ca2+ and the conformational changes of the receptor.
Article
Engineering, Electrical & Electronic
Evan Seitz, Francisco Acosta-Reyes, Suvrajit Maji, Peter Schwander, Joachim Frank
Summary: This study is based on the manifold-embedding approach to study biological molecules with continuous conformational changes. A novel framework called ESPER has been developed, which can retrieve the free-energy landscape and 3D Coulomb potential maps for all simulated states. ESPER shows substantial improvements compared to previous work in reconstructing 3D movies and exploring free-energy landscapes.
IEEE TRANSACTIONS ON COMPUTATIONAL IMAGING
(2022)
Review
Biochemistry & Molecular Biology
Kira DeVore, Po-Lin Chiu
Summary: Single-particle cryogenic electron microscopy (cryo-EM) has become an indispensable tool for investigating high-resolution structural details of biomolecules. It allows for direct visualization of biomolecules and the reconstruction of a three-dimensional Coulomb potential density map through averaging molecular images. New algorithms have been developed to analyze the structural heterogeneity from massive and low signal-to-noise-ratio (SNR) cryo-EM datasets, expanding our understanding of the multiple conformational states and dynamics of the target biomolecules.
Article
Biochemistry & Molecular Biology
Kunio Nakata, Naoyuki Miyazaki, Hiroki Yamaguchi, Mika Hirose, Tatsuki Kashiwagi, Nidamarthi H. Kutumbarao, Osamu Miyashita, Florence Tama, Hiroshi Miyano, Toshimi Mizukoshi, Kenji Iwasaki
Summary: The three-dimensional structure of phosphoketolase (PKT) from Bifidobacterium longum was determined using cryo-EM single-particle analysis. The study observed interesting structural features and multiple conformations of amino acid residues, as well as the presence of water molecules. The conformational changes of the QN-loop were found to be related to the enzymatic function of PKT.
JOURNAL OF STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Wooyoung Choi, Hao Wu, Klaus Yserentant, Bo Huang, Yifan Cheng
Summary: CRISPR/Cas9-based genome engineering has greatly enhanced our ability to manipulate biological systems, and researchers have now developed a strategy to efficiently tag endogenous proteins in human cell lines using this technology. This tagging approach, combined with advancements in single-particle cryogenic electron microscopy, allows for effective structural studies of native proteins in their natural cellular environment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Ashraya Ravikumar, Mrugsen Nagsen Gopnarayan, Sriram Subramaniam, Narayanaswamy Srinivasan
Summary: This study evaluates systematic differences in local structure and conformation within protein tertiary structures determined by crystallography and cryo-EM. The results show that cryo-EM structures have more dispersed side chains compared to X-ray crystallography structures of similar resolution. This trend is observed in both subunit interface packing and within the core of tertiary structures. The reduced dispersion of side chains in protein crystals could be attributed to dehydration in 3D crystals prepared for X-ray crystallography, while the higher freezing rate in cryo-EM samples may preserve a more native conformation.
Article
Multidisciplinary Sciences
Shanshan Li, Michael Z. Palo, Grigore Pintilie, Xiaojing Zhang, Zhaoming Su, Kalli Kappel, Wah Chiu, Kaiming Zhang, Rhiju Das
Summary: The Tetrahymena group I intron has provided valuable insights into the folding and misfolding of RNA. In this study, cryo-EM was used to visualize the misfolded structures of the Tetrahymena L-21 ScaI ribozyme. Multiple misfolded substates were identified and compared to the native state, revealing topological differences that explain the failure of substrate docking and suggest pathways for refolding.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biophysics
Deryck J. Mills
Summary: Cryo-electron microscopy is now the preferred technique for structural biology of macromolecular assemblies, achieving resolutions better than 2 angstrom. Proper instruments and cooperative samples are essential for collecting high-quality images.
QUARTERLY REVIEWS OF BIOPHYSICS
(2021)