Article
Multidisciplinary Sciences
Xian Zhou, Chen-Jun Guo, Chia-Chun Chang, Jiale Zhong, Huan-Huan Hu, Guang-Ming Lu, Ji-Long Liu
Summary: CTPS activity is regulated by the binding of nucleotides and glutamine, with GTP directly blocking ammonia leakage and stabilizing the ammonia tunnel. Cryo-electron microscopy revealed the binding modes of substrates and analogs in Drosophila CTPS, providing insights into allosteric regulation and CTP synthesis mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
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
Chen-Jun Guo, Ji-Long Liu
Summary: The nucleotide CTP can be synthesized de novo from UTP via the metabolic enzyme CTP synthase (CTPS). It has been discovered in recent years that CTPS can form snake-shaped mesoscale cytoophidia in fruit fly cells, which are undetectable under light microscopy. This review summarizes the current understanding of cytoophidia and filaments formed by CTPS, including their conservation, morphology, and functions.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
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
Biochemistry & Molecular Biology
Wim J. H. Hagen
Summary: Researchers have presented an energy filter-based plasmon imaging method for rapid screening of gold foil grids, in order to save expensive imaging time.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Multidisciplinary Sciences
Domen Kampjut, Julia Steiner, Leonid A. Sazanov
Summary: Our study systematically investigated the effects of buffer components, blotting conditions, and grid types on membrane protein grid preparation. We found that aggregation was a common issue, which could be addressed by adjusting detergents, salt concentration, or reconstitution methods. Furthermore, we discussed strategies for achieving optimal ice thickness, particle coverage, and orientation distribution on both free ice and support films. Our findings provide a clear roadmap for comprehensive screening of conditions for cryo-EM grid preparation of membrane proteins.
Article
Biology
Fumiya K. Sano, Hiroaki Akasaka, Wataru Shihoya, Osamu Nureki, David Drew
Summary: This study reports the structure of the complex between the endothelin ETB receptor and G-protein, revealing how endothelin activates the ETB receptor and expanding the diversity of G-protein binding modes.
Article
Multidisciplinary Sciences
Qi Jia, Ye Xiang
Summary: In this study, the cryo-EM structure of a M13 mini variant bacteriophage was reported. The mini phage has two cap-like complexes at its distal ends, formed by minor coat proteins. The inner single stranded DNA genome adopts a helical structure similar to double-stranded DNA.
NATURE COMMUNICATIONS
(2023)
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)
Article
Multidisciplinary Sciences
Anjie Xia, Xihao Yong, Changbin Zhang, Guifeng Lin, Guowen Jia, Chang Zhao, Xin Wang, Yize Hao, Yifei Wang, Pei Zhou, Xin Yang, Yue Deng, Chao Wu, Yujiao Chen, Jiawei Zhu, Xiaodi Tang, Jingming Liu, Shiyu Zhang, Jiahao Zhang, Zheng Xu, Qian Hu, Jinlong Zhao, Yuting Yue, Wei Yan, Zhaoming Su, Yuquan Wei, Rongbin Zhou, Haohao Dong, Zhenhua Shao, Shengyong Yang
Summary: This study presents the cryo-EM structures of GPR34 bound with LysoPS and its inhibition by the antagonist YL-365. The findings provide mechanistic insights into the endogenous agonist recognition and antagonist inhibition of GPR34, highlighting GPR34 as a promising target for disease treatment.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Oncology
Han-Chao Feng, Christos Andreadis, Ji-Long Liu
Summary: The formation of cytoophidia in fission yeast is influenced by the histone chaperone Slm9, as knockout of the slm9 gene leads to fragmentation and changes in morphology of the cytoophidia. This study reveals a potential link between a chromosomal regulatory factor and cytoophidium biogenesis.
EXPERIMENTAL CELL RESEARCH
(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.
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)
Article
Multidisciplinary Sciences
Xiao Fan, Jian Huang, Xueqin Jin, Nieng Yan
Summary: Voltage-gated sodium channel Nav1.6 is crucial for neuronal firing and its dysfunction can lead to epilepsy and neurological disorders. The cryo-EM structure of human Nav1.6 reveals its inactivated state with closed pore domain and all up voltage-sensing domains. The presence of an unidentified molecule bound to the Nav1.6 PD suggests a potential target for developing specific blockers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Meng-Ru Ho, Yi-Ming Wu, Yen-Chen Lu, Tzu-Ping Ko, Kuen-Phon Wu
Summary: In this study, a cryo-electron microscopy (cryo-EM) structure of a 723-amino acid protein called malate synthase G (MSG) from Escherichia coli was determined at a resolution of 2.9 A. The cryo-EM structure of this 82-kDa protein was found to be similar to structures resolved by X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, with no distinguishable differences. The study also revealed consistent conformational flexibilities among different experimental approaches, particularly in the alpha/beta domain. Additionally, differences in sidechain rotations of certain residues involved in hosting the cofactor acetyl-CoA and substrate were observed between the cryo-EM apo-form and complex crystal structures. These findings demonstrate that cryo-EM can be used to determine the structures and conformational heterogeneity of sub-100 kDa biomolecules with a quality comparable to X-ray crystallography and NMR spectroscopy.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Eric M. Lynch, Justin M. Kollman
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2020)
Article
Biology
Jacqueline C. Simonet, Maya J. Foster, Eric M. Lynch, Justin M. Kollman, Emmanuelle Nicholas, Alana M. O'Reilly, Jeffrey R. Peterson
Review
Cell Biology
Eric M. Lynch, Justin M. Kollman, Bradley A. Webb
CURRENT OPINION IN CELL BIOLOGY
(2020)
Article
Multidisciplinary Sciences
Chunfu Xu, Peilong Lu, Tamer M. Gamal El-Din, Xue Y. Pei, Matthew C. Johnson, Atsuko Uyeda, Matthew J. Bick, Qi Xu, Daohua Jiang, Hua Bai, Gabriella Reggiano, Yang Hsia, T. J. Brunette, Jiayi Dou, Dan Ma, Eric M. Lynch, Scott E. Boyken, Po-Ssu Huang, Lance Stewart, Frank DiMaio, Justin M. Kollman, Ben F. Luisi, Tomoaki Matsuura, William A. Catterall, David Baker
Article
Immunology
Christopher D. Thouvenel, Mary F. Fontana, Jason Netland, Akshay T. Krishnamurty, Kennidy K. Takehara, Yu Chen, Suruchi Singh, Kazutoyo Miura, Gladys J. Keitany, Eric M. Lynch, Silvia Portugal, Marcos C. Miranda, Neil P. King, Justin M. Kollman, Peter D. Crompton, Carole A. Long, Marie Pancera, David J. Rawlings, Marion Pepper
Summary: This study demonstrates the potential of high-avidity IgM antibodies in both therapeutics and vaccines. Forced multimerization of IgG antibodies significantly improved antigen binding and parasite restriction, highlighting how avidity can alter antibody function.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Anika L. Burrell, Daniel P. Farrell, Jianming Kang, Meiling Wang, Jesse M. Hansen, Alex Pravat, Lisa M. Tuttle, Mikaela D. Stewart, Peter S. Brzovic, Champak Chatterjee, Weixing Zhao, Frank DiMaio, Justin M. Kollman, Rachel E. Klevit
Summary: Mutations in the RING domains of the E3 ubiquitin ligase BRCA1/BARD1 increase the risk of breast and ovarian cancers. The structure of the BRCA1/BARD1 RING heterodimer with UbcH5c bound to the nucleosome, along with biochemical data, explains how the complex selectively ubiquitylates specific lysines in H2A. The findings provide insight into how E3 ligases target lysine residues in nucleosomes and how mutations in cancer patients affect this process.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Neri Amara, Madison P. Cooper, Maria A. Voronkova, Bradley A. Webb, Eric M. Lynch, Justin M. Kollman, Taylur Ma, Kebing Yu, Zijuan Lai, Dewakar Sangaraju, Nobuhiko Kayagaki, Kim Newton, Matthew Bogyo, Steven T. Staben, Vishva M. Dixit
Summary: The study demonstrates that small-molecule LDC7559 and its potent analog NA-11 inhibit the NOX2-dependent oxidative burst in neutrophils by activating PFKL, reducing inflammation and tissue damage. This provides a potential tool for selectively activating PFKL, the main isoform expressed in immune cells.
Article
Biology
Jesse M. Hansen, Avital Horowitz, Eric M. Lynch, Daniel P. Farrell, Joel Quispe, Frank DiMaio, Justin M. Kollman
Summary: Many metabolic enzymes can self-assemble into filaments to organize and regulate metabolism, with this process often coinciding with significant metabolic changes. In yeast, cytoplasmic acidification upon starvation triggers the assembly of many metabolic enzymes into filaments, including CTPS. The assembly mechanism of CTPS is pH-sensitive and is conserved across different species.
Article
Multidisciplinary Sciences
A. Courbet, J. Hansen, Y. Hsia, N. Bethel, Y-J Park, C. Xu, A. Moyer, S. E. Boyken, G. Ueda, U. Nattermann, D. Nagarajan, D-A Silva, W. Sheffler, J. Quispe, A. Nord, N. King, P. Bradley, D. Veesler, J. Kollman, D. Baker
Summary: This study explores the construction of protein machinery by designing axle and rotor components, achieving successful assembly in vitro and in vivo, and demonstrating a new approach to protein structure construction.
Article
Multidisciplinary Sciences
Agatha Lyczek, Benedict-Tilman Berger, Aziz M. Rangwala, YiTing Paung, Jessica Tom, Hannah Philipose, Jiaye Guo, Steven K. Albanese, Matthew B. Robers, Stefan Knapp, John D. Chodera, Markus A. Seeliger
Summary: Protein kinase inhibitors are potent anticancer drugs, but some patients develop resistance to these inhibitors, leading to suboptimal treatment outcomes. Mutations in the Bcr-Abl kinase domain contribute to resistance, with some altering drug-protein interactions and others located far from the drug-binding site still conferring resistance.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)