Article
Multidisciplinary Sciences
Gabriel Schuler, Chunyi Hu, Ailong Ke
Summary: The Class 2 CRISPR effectors Cas9 and Cas12 may have evolved from nucleases in IS200/IS605 transposons. A study reported a cryo-electron microscopy structure of IscB-omega RNA bound to a dsDNA target, revealing the similarities between IscB and Cas9 ribonucleoproteins and explaining the mechanisms of target recognition, R-loop formation, and DNA cleavage.
Article
Multidisciplinary Sciences
Shabareesh Pidathala, Aditya Kumar Mallela, Deepthi Joseph, Aravind Penmatsa
Summary: The researchers used the Drosophila melanogaster dopamine transporter as a surrogate to study the structure and function of norepinephrine, revealing potential paradigms for designing chronic pain inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ying Xia, Chun-Qiu Xia, Xiaoyong Pan, Hong-Bin Shen
Summary: The paper proposes GraphBind, an accurate predictor for identifying nucleic-acid-binding residues on proteins based on an end-to-end graph neural network. By constructing graphs based on structural contexts and using hierarchical graph neural networks to embed local patterns, GraphBind demonstrates superior performance in binding residue recognition.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Chemistry, Inorganic & Nuclear
P. David Dayanidhi, V. G. Vaidyanathan
Summary: Metal complexes have been studied as structural probes for nucleic acids due to their excellent photophysical/chemical properties, offering a new avenue for developing novel drugs and diagnostic tools targeting DNA defects. By changing the ligand structure or metal center, the probing efficiency of metal complexes towards defects can vary, providing potential insights for future directions in this field.
DALTON TRANSACTIONS
(2021)
Article
Chemistry, Multidisciplinary
Huasong Ai, Guo-Chao Chu, Qingyue Gong, Ze-Bin Tong, Zhiheng Deng, Xin Liu, Fan Yang, Ziyu Xu, Jia-Bin Li, Changlin Tian, Lei Liu
Summary: The chemical synthesis of homogeneously modified histones is a powerful approach to deciphering how post-translational modifications modulate epigenetic events. In this study, we developed a rapid method to synthesize phosphorylated and ubiquitinated H2AX proteins and found that H2AXS139 phosphorylation distorts the interaction interface between ubiquitin and the repair factor 53BP1. Our study revealed redundancy in the interplay of multiple histone PTMs, which is useful for controlling the dynamic distribution of effector proteins on nucleosomes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Cell Biology
Peiyu Xu, Sijie Huang, Brian E. Krumm, Youwen Zhuang, Chunyou Mao, Yumu Zhang, Yue Wang, Xi-Ping Huang, Yong-Feng Liu, Xinheng He, Huadong Li, Wanchao Yin, Yi Jiang, Yan Zhang, Bryan L. Roth, H. Eric Xu
Summary: The dopaminergic system and its receptors (D1R to D5R) have important roles in the central nervous system. This study presents cryo-EM structures of all five subtypes of human dopamine receptors complexed with G protein and the pan-agonist rotigotine. The structures provide insight into rotigotine recognition, ligand polypharmacology, receptor activation, unique receptor subtype features, and G protein coupling specificity. This work offers a comprehensive set of structural templates for the development of specific ligands to target dopaminergic system-related CNS diseases.
Article
Biochemical Research Methods
Alexander Mitrofanov, Marcus Ziemann, Omer S. Alkhnbashi, Wolfgang R. Hess, Rolf Backofen
Summary: This study introduces a new pipeline, CRISPRtracrRNA, for screening and evaluating tracrRNA candidates in genomes. The pipeline combines evidence from different components of the Cas9-sgRNA complex. It also utilizes a newly developed structural model to simulate the structure of tracrRNA. Additionally, evidence is provided through the detection of repeat sequences, terminator signals, and RNA-RNA interactions.
Article
Biochemistry & Molecular Biology
Sagar Satpathi, Tamaki Endoh, Peter Podbevsek, Janez Plavec, Naoki Sugimoto
Summary: The study demonstrates detailed interaction analysis between PCs and RNAs to verify the impact of PCs on RNA functions, using berberine as a model PC. It identifies a minimal RNA motif interacting with berberine and highlights the importance of electrostatic and stacking interactions for sequence selective interaction and RNA stabilization. This selective interaction with a relatively small RNA motif based on a chemical structure of a planer heterocyclic highlights the biological activities of various PCs mediated by interactions with functional RNAs.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Chemistry, Analytical
Julien Camperi, Maryam Moshref, Lu Dai, Ho Young Lee
Summary: Advances in gene-editing technology have allowed efficient ex vivo engineering of different cell types, offering a potential therapeutic platform for challenging diseases. The quality of Cas9 protein and sgRNA affects the formation, stability, and functional activity of Cas9 RNP complexes, with heated sgRNA leading to higher rates of double-strand DNA cleavage in the Cas9 RNP complexes.
ANALYTICAL CHEMISTRY
(2022)
Article
Biology
Kangcheng Song, Miao Wei, Wenjun Guo, Li Quan, Yunlu Kang, Jing-Xiang Wu, Lei Chen
Summary: TRPC5 channel is a nonselective cation channel involved in various physiological processes. Inhibitors of TRPC5, such as clemizole and HC-070, stabilize the ion channel in a nonconductive closed state, potentially offering new therapeutic strategies for anxiety disorders, depression, and kidney diseases. The cryo-EM structures of human TRPC5 with inhibitors provide insights into the binding sites and inhibitory mechanisms, facilitating the development of more effective inhibitors targeting TRPC5.
Article
Biochemistry & Molecular Biology
Lilei Xu, Yu Xiao, Jie Zhang, Xianyang Fang
Summary: In bacteria, the expression of folate-related genes is controlled by different types of riboswitches, including the THF-I and recently discovered THF-II riboswitches. In this study, the crystal structures of THF-II riboswitch from Mesorhizobium loti were determined, revealing a unique architecture stabilized by continuous base pair stacking. The ligand binding pocket of the riboswitch accommodates the pterin moiety and its binding is influenced by Mg2+ ions. Ligand binding reduces accessibility of the ribosome binding site, regulating the expression of downstream genes. These findings provide mechanistic insights into translation regulation by THF-II riboswitch.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Gaofeng Cui, Maria Victoria Botuyan, Pascal Drane, Qi Hu, Benoit Bragantini, James R. Thompson, David J. Schuller, Alexandre Detappe, Michael T. Perfetti, Lindsey I. James, Stephen V. Frye, Dipanjan Chowdhury, Georges Mer
Summary: This study reveals an autoinhibited state of 53BP1 that hinders its ability to bind to chromatin. Small molecule ligands present a potential avenue for the development of cancer therapy drugs.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Qin Gong, Kim Robinson, Chenrui Xu, Phuong Thao Huynh, Kelvin Han Chung Chong, Eddie Yong Jun Tan, Jiawen Zhang, Zhao Zhi Boo, Daniel Eng Thiam Teo, Kenneth Lay, Yaming Zhang, John Soon Yew Lim, Wah Ing Goh, Graham Wright, Franklin L. Zhong, Bruno Reversade, Bin Wu
Summary: NLRP1 and CARD8 are two recently characterized sensor proteins for the human inflammasome complex. The cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. The authors propose a two-step model for NLRP1 activation.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Liu-Yi Liu, Tian-Zhu Ma, You-Liang Zeng, Wenting Liu, Zong-Wan Mao
Summary: This study reveals the structural basis for the specific recognition of G-quadruplex (G4) by pyridostatin (PDS) and its derivatives. The results demonstrate that the rigid aromatic rings of PDS linked by flexible amide bonds match adaptively with G-tetrad planes, enhancing p-p stacking and achieving specific recognition of G4s. The aliphatic amine side chains of PDS adjust conformation to interact with the phosphate backbone via hydrogen bonding and electrostatic interactions, increasing affinity for G4s.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Multidisciplinary Sciences
Amika Kikuchi, Hiroki Onoda, Kosuke Yamaguchi, Satomi Kori, Shun Matsuzawa, Yoshie Chiba, Shota Tanimoto, Sae Yoshimi, Hiroki Sato, Atsushi Yamagata, Mikako Shirouzu, Naruhiko Adachi, Jafar Sharif, Haruhiko Koseki, Atsuya Nishiyama, Makoto Nakanishi, Pierre-Antoine Defossez, Kyohei Arita
Summary: In this study, we report the cryo-EM structure of DNMT1 bound to its natural activators, providing a mechanistic basis for DNMT1 activation. The findings reveal a previously unstudied linker playing a key role in the activation process and highlight the importance of this activation mechanism for basic research and drug design.
NATURE COMMUNICATIONS
(2022)
