Article
Biochemistry & Molecular Biology
Migle Kisonaite, Klemens Wild, Karine Lapouge, Genis Valentin Gese, Nikola Kellner, Ed Hurt, Irmgard Sinning
Summary: The authors used cryo-EM to investigate how the RAC complex, a conserved ribosome-associated chaperone triad, assists in cotranslational protein folding. They determined cryo-EM structures of RAC bound to 80S ribosomes, revealing two distinct conformations and a tight interaction between the RAC components. They also discovered a non-canonical interaction that masks the HPD motif in the J domain protein Zuo1, allowing proper positioning of Ssb for activation. These findings provide insights into the dynamic interaction and protein folding process involving RAC and Ssb.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Peng-yue Zhao, Ren-qi Yao, Zi-cheng Zhang, Sheng-yu Zhu, Yu-xuan Li, Chao Ren, Xiao-hui Du, Yong-ming Yao
Summary: Protein homeostasis is crucial for various life activities, and ribosomes, as the main apparatus of protein translation, play an essential role in maintaining protein homeostasis. However, malfunction of ribosomes can lead to the excessive production and accumulation of aberrant proteins, causing harmful effects on cellular fate and even cell death. Ribosomopathies are a group of diseases characterized by abnormalities in ribosomal compositions and functions, and cells have evolved ribosome quality control mechanisms to regulate the quantity and quality of ribosomes.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2022)
Article
Multidisciplinary Sciences
Jae Ho Lee, Ahmad Jomaa, SangYoon Chung, Yu-Hsien Hwang Fu, Ruilin Qian, Xuemeng Sun, Hao-Hsuan Hsieh, Sowmya Chandrasekar, Xiaotian Bo, Simone Mattei, Daniel Boehringer, Shimon Weiss, Nenad Ban, Shu-ou Shan
Summary: The signal recognition particle (SRP) plays a key role in delivering proteins to the endoplasmic reticulum in eukaryotic cells, and its transition from cargo recognition to protein translocation involves multiple conformational rearrangements initiated by GTPase-driven processes. Disruption of these rearrangements, particularly in disease-linked mutants, can affect the SRP/SR GTPase cycle. This study provides insights into the molecular basis of early SRP-SR recognition and highlights the importance of eukaryote-specific elements in targeting regulation.
Article
Physics, Fluids & Plasmas
Peng Tao, Yi Xiao
Summary: The correct folding of proteins is crucial for their functions, and cotranslational folding is a vital mechanism for achieving proper folding. Previous studies have shown that cotranslational folding can improve folding efficiency, but its detailed mechanism is still unclear. In this study, molecular dynamics simulations were used to investigate the cotranslational folding of three beta-sheet-enriched proteins. The results demonstrate that cotranslational folding can enhance the helical population and reduce non-native long-range contacts before emerging from the ribosomal exit tunnel.
Article
Multidisciplinary Sciences
Michael R. Lawson, Laura N. Lessen, Jinfan Wang, Arjun Prabhakar, Nicholas C. Corsepius, Rachel Green, Joseph D. Puglisi
Summary: Through single-molecule fluorescence assays, researchers found that in the termination process of yeast translation, the two release factors eRF1 and eRF3 bind together to rapidly recognize stop codons and induce termination through a tightly regulated, multistep process that resembles transfer RNA selection during translation elongation.
Article
Biotechnology & Applied Microbiology
Evan M. Zhao, Angelo S. Mao, Helena de Puig, Kehan Zhang, Nathaniel D. Tippens, Xiao Tan, F. Ann Ran, Isaac Han, Peter Q. Nguyen, Emma J. Chory, Tiffany Y. Hua, Pradeep Ramesh, David B. Thompson, Crystal Yuri Oh, Eric S. Zigon, Max A. English, James J. Collins
Summary: The use of eukaryotic toehold switches (eToeholds) allows for efficient induction of gene translation in eukaryotic cells, capable of distinguishing the presence of RNA transcripts under various circumstances. Through optimization of RNA annealing, up to 16-fold induction of transgene expression was achieved.
NATURE BIOTECHNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Dejiu Zhang, Lei Zhu, Fei Wang, Peifeng Li, Yin Wang, Yanyan Gao
Summary: Converting genetic information into functional proteins is a complex process that needs to be accurately regulated. Recent advancements in biotechnology have provided a better understanding of the mechanisms of protein translation fidelity. This review focuses on the regulatory mechanisms of eukaryotic ribosomes and translation factors in ensuring translation accuracy, as well as the diseases that can arise from translation errors.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemistry & Molecular Biology
Eric Westhof, Bryan Thornlow, Patricia P. Chan, Todd M. Lowe
Summary: Metazoan organisms have highly conserved tRNA sequence motifs, despite the presence of a large number of tRNA genes. Non-Watson-Crick base pairs, especially GoU pairs, play important roles in the structure and function of tRNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Oncology
Simone Pellegrino, Salvatore Terrosu, Gulnara Yusupova, Marat Yusupov
Summary: Understanding the molecular basis of ribosomal inhibition by small molecules is essential for developing potential anticancer drugs. Recent advancements in structural studies have shed light on the binding modes of ribosome inhibitors, providing valuable insights for the development of more potent and specific treatments for cancer cells.
Article
Biology
Dominik Layer, Juergen Kopp, Miriam Fontanillo, Maja Koehn, Karine Lapouge, Irmgard Sinning
Summary: Layer et al. present a crystal structure of Naa20, the catalytic subunit of an N-terminal acetyltransferase NatB, in complex with its competitive inhibitor CoA-Ac-MDEL. They find that Naa20 alone can acetylate NatB in vitro while Naa25, the auxiliary subunit of Naa20, increases the substrate affinity of Naa20. This study provides insights into the development of NAT inhibitors.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Matthias Thoms, Benjamin Lau, Jingdong Cheng, Lisa Fromm, Timo Denk, Nikola Kellner, Dirk Flemming, Paulina Fischer, Laurent Falquet, Otto Berninghausen, Roland Beckmann, Ed Hurt
Summary: The study isolated and described the conserved rixosome from Chaetomium thermophilum, which consists of two sub-modules, Rix1-Ipi3-Ipi1 and Las1-Grc3 complex. The Rix1 complex plays a key role in pre-60S particles by inserting between the 5S rRNA tip and L1-stalk, facilitating the rotation of immature 5S RNP. The other sub-module with Las1 endonuclease and Grc3 polynucleotide-kinase cleaves and phosphorylates the nearby ITS2 pre-rRNA at the pre-60S foot. Inward movement of the L1 stalk permits the Nop53 N-terminus with AIM motif to participate in completing ITS2 removal.
Article
Biochemistry & Molecular Biology
Paul Powell, Usha Bhardwaj, Dixie Goss
Summary: This study identifies secondary structures that selectively interact with eIF3 and explores its role in translation initiation of BYDV. The findings propose a new model for BYDV translation initiation and expand the known functionality of eIF3.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Caillan Crowe-McAuliffe, Hiraku Takada, Victoriia Murina, Christine Polte, Sergo Kasvandik, Tanel Tenson, Zoya Ignatova, Gemma C. Atkinson, Daniel N. Wilson, Vasili Hauryliuk
Summary: In all branches of life, stalled translation intermediates are recognized and processed by ribosome-associated quality control pathways. The process involves splitting of stalled ribosomes and targeting incomplete proteins for degradation by NEMF family proteins. Structural analysis reveals the mechanism of C-terminal tailing in Bacillus subtilis, mediated by NEMF protein RqcH and RqcP, in synthesizing polypeptides in the absence of mRNA or the small subunit.
Article
Biochemistry & Molecular Biology
Jing Wang, Yuka Yashiro, Yuriko Sakaguchi, Tsutomu Suzuki, Kozo Tomita
Summary: CdiA-CTEC869 cleaves specific tRNAs by interacting with translation factors Tu and Ts, and interacts with domain II of Tu to affect the structure and cleavage efficiency of tRNAs.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Masoumeh Rezaei-Moshaei, Ali Dehestani, Ali Bandehagh, Ali Pakdin-Parizi, Majid Golkar, Reza Heidari-Japelaghi
Summary: In this study, a new type 2 RIP sequence (pebulin) was isolated and cloned from dwarf elder native to Iran. The recombinant pebulin protein was expressed in E. coli with the help of a chaperone plasmid and low temperature incubation to enhance solubility. Hemagglutination, anticancer, and antifungal assays showed that pebulin agglutinated erythrocytes, inhibited cancer cell proliferation, and had growth-inhibiting effects against plant pathogenic fungi.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biology
Xia Wang, Jiaxuan Cheng, Jiawei Shen, Liguo Liu, Ningning Li, Ning Gao, Feng Jiang, Qi Jin
Summary: The extracellular contractile injection systems (eCISs) are present in the genomes of many bacteria and archaea, with Photorhabdus Virulence Cassette (PVC) being a typical member. PVC delivers effectors directly into mammalian macrophages by loading them into the inner tube and injecting them into the cells, disrupting dNTP pools and actin cytoskeleton formation to kill the target cells.
SCIENCE CHINA-LIFE SCIENCES
(2022)
Article
Cell Biology
Chengying Ma, Chengkun Wang, Dingyi Luo, Lu Yan, Wenxian Yang, Ningning Li, Ning Gao
Summary: Lateral segregation of membrane constituents into functional microdomains, known as lipid rafts, is a universal principle for cellular membranes. SPFH proteins may play a scaffolding role and regulate specific processes on the membrane. The structure of a supramolecular complex involving SPFH proteins and a membrane-anchored protease has been reported, providing mechanistic insights into their role in membrane organization and functionalization.
Article
Multidisciplinary Sciences
Xin Hu, Shuangying Jiang, Feifei Xu, Cheng Zeng, Xiangxiang Wang, Wei Liu, Aimin Cheng, Chengying Ma, Ning Gao, Yuyu Zhao, Junbiao Dai, Guanghou Zhao
Summary: Emerging evidence suggests that ribosomes are dynamic machines with heterogeneous protein compositions, and their abilities to translate and adapt to environmental changes can be reshaped. Duplications of ribosomal protein genes affect cell function through gene dose amplification and paralog-specific regulation, providing robustness and phenotypic plasticity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Ningning Li, Ning Gao, Yuanliang Zhai
Summary: DNA replication in eukaryotes is regulated by replication licensing and origin firing processes, driven by CDK and DDK kinases, respectively. Recent cryo-electron microscopy studies have provided structural insights into the assembly and remodeling of replication initiation machineries, including the MCM-DH-DDK complex, revealing mechanisms of kinase activation and substrate recognition.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Correction
Multidisciplinary Sciences
Chengying Ma, Damu Wu, Qian Chen, Ning Gao
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Yan Liu, Zihan Wu, Damu Wu, Ning Gao, Jinzhong Lin
Summary: A Ribozyme-Assisted Polycistronic co-expression system (pRAP) was developed for heterologous co-production and in vivo assembly of multi-subunit complexes. The system allows balanced expression of subunits, allowing faithful protein complex assembly. Successful reconstitution of large functional multi-subunit complexes validates the utility of pRAP for studying biological processes.
ACS SYNTHETIC BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Damu Wu, Yan Liu, Yuhao Dai, Guopeng Wang, Guoliang Lu, Yan Chen, Ningning Li, Jinzhong Lin, Ning Gao, Richard Hodge
Summary: The human AAA+ ATPase CLPB is a protein disaggregase in the mitochondrial intermembrane space and plays a role in promoting the solubilization of mitochondrial proteins. Structural characterization reveals that CLPB forms different oligomers depending on its state and contains an ANK domain essential for its disaggregase activity. Interactome analysis suggests that the ANK domain may directly interact with various mitochondrial substrates. These findings highlight the unique properties of CLPB and its potential as a therapeutic target for mitochondria-related diseases.
Article
Biochemistry & Molecular Biology
Ningning Li, Siyi Chen, Kui Xu, Meng -Ting He, Meng-Qiu Dong, Qiangfeng Cliff Zhang, Ning Gao
Summary: The spectrin-based membrane skeleton is a crucial component of metazoan cells, and mutations in its proteins can lead to various human diseases. This study presents the cryo-EM structures of the spectrin-actin junctional complex, revealing its organization and interactions. The findings provide a structural basis for understanding the assembly and dynamics of the membrane skeleton and shed light on the mechanisms of F-actin-binding factors in other systems.
Article
Multidisciplinary Sciences
Zongqiang Li, Shuaijiabin Chen, Liang Zhao, Guoqiang Huang, Huiqin Xu, Xiaoyun Yang, Peiyi Wang, Ning Gao, Sen-Fang Sui
Summary: The nuclear pore complex (NPC) mediates the exchange of macromolecules between the nucleus and cytoplasm. The cryo-electron microscopy structure of native pre-60S particles trapped in yeast NPCs reveals multiple export factors and their interactions with the NPC's phenylalanine-glycine (FG) repeats, facilitating the passage of pre-60S particles through the NPC. In addition, the distribution analysis shows that up to four pre-60S particles can be accommodated by a single NPC, with enrichment in the inner ring regions close to the wall.
Article
Biochemistry & Molecular Biology
Soubhagyalaxmi Jema, Chu Chen, Lauren Humphrey, Shriya Karmarkar, Frank Ferrari, Ajit P. Joglekar
Summary: During mitosis, the recruitment of SAC signaling proteins to kinetochores plays a crucial role in preventing chromosome missegregation. This study reveals that the cellular abundance of the SAC signaling protein Bub1 limits its own recruitment and that of BubR1, thereby regulating the SAC signaling activity. The number of SAC proteins recruited by a signaling kinetochore is inversely correlated with the total number of signaling kinetochores in the cell.
Article
Cell Biology
Yunyang Zhang, Xiaomeng Liang, Sha Luo, Yan Chen, Yu Li, Chengying Ma, Ningning Li, Ning Gao
Summary: Eukaryotic ribosome assembly is a complex process involving numerous protein factors. This study presents high-resolution cryo-EM structures of nuclear pre-60S particles from human cells, revealing the hierarchical assembly pathway and the role of certain factors as rRNA chaperones. The findings provide important insights into the fine details of the assembly process and contribute to the understanding of ribosome maturation.