Article
Plant Sciences
Gerard Vergoten, Christian Bailly
Summary: Cryptoconcatones A-L is a series of 12 dihydropyrone derivatives isolated from the evergreen tree Cryptocarya concinna Hance, with potential antiproliferative activity against cancer cells. In this study, the interaction of these compounds with tubulin dimers was investigated using molecular docking. Two compounds, cryptoconcatones F and L, showed stronger binding capacity to alpha-tubulin than pironetin, a known microtubule polymerization inhibitor. The study contributes to the understanding of the mechanism of action of cryptoconcatones and may aid in the design of analogues targeting the pironetin site of alpha-tubulin.
Article
Multidisciplinary Sciences
Diogjena Katerina Prifti, Annie Lauzier, Sabine Elowe
Summary: TEM4 is a critical protein involved in the regulation of cytoskeleton and plays essential roles in cell migration, cell-cell junction formation, and mitosis. However, a commonly used TEM4 antibody in Western blotting and immunocytochemistry also cross-reacts with NuMA, which may affect the interpretation of experiments using this antibody probe.
Article
Neurosciences
Samanta Mazzetti, Alessandra M. Calogero, Gianni Pezzoli, Graziella Cappelletti
Summary: This paragraph discusses the interplay between alpha-synuclein and the microtubule cytoskeleton in neurodegenerative diseases. Alpha-synuclein is a key protein involved in neurodegeneration, and its interaction with other proteins and structures makes it difficult to identify the trigger for neuronal death. The imbalance of the microtubule cytoskeleton is emerging as a convergence point in neurodegeneration. Alpha-synuclein and microtubules have been shown to interact and communicate with other intracellular structures.
EXPERIMENTAL NEUROLOGY
(2023)
Article
Cell Biology
Wenfeng Feng, Rong Liu, Xuan Xie, Lei Diao, Nannan Gao, Jinke Cheng, Xu Zhang, Yong Li, Lan Bao
Summary: The newly discovered SUMOylation on alpha-tubulin is an important posttranslational modification that affects microtubule properties and cellular functions. SUMOylation can promote microtubule catastrophe, interfere with its polymerization process, and inhibit the assembly of alpha-tubulin into microtubules.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2021)
Article
Cell Biology
Jose Martinez-Hernandez, Julie Parato, Aditi Sharma, Jean-Marc Soleilhac, Xiaoyi Qu, Ellen Tein, Andrew Sproul, Annie Andrieux, Yves Goldberg, Marie-Jo Moutin, Francesca Bartolini, Leticia Peris
Summary: This study found an accumulation of tubulin acetylation in post-mortem brain tissues from Alzheimer's disease patients and human neurons with the Alzheimer's familial APP-V717I mutation. Impaired tubulin re-tyrosination may contribute to this acetylation accumulation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Abesh Bera, Mohan L. Gupta
Summary: Microtubules are dynamic polymers assembled from alpha- and beta-tubulin subunits, with diverse properties determined by different tubulin isotypes and posttranslational modifications. Research in microorganisms has provided valuable insights into the distinct properties of tubulin isotypes and their roles in facilitating specific cellular processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Chuanyan Yang, Xuezhu Chen, Chenxu Zhang, Xuejiao Lei, Yongling Lu, Yuhai Wang, Hua Feng, Tunan Chen, Yang Yang
Summary: This study aimed to investigate whether the upregulation of acetylated α-tubulin (a-Ac-Tub) could alleviate injury to dendritic spines in the penumbra area and motor dysfunction after ischemic stroke. Knockout of MEC17, the specific acetyltransferase of a-tubulin, in pyramidal neurons exacerbated dendritic spine injury and motor dysfunction after stroke. However, upregulation of MEC17 and treatment with tubastatin A (TBA) maintained mature dendritic spine density and alleviated motor dysfunction after stroke.
CNS NEUROSCIENCE & THERAPEUTICS
(2023)
Article
Agronomy
Jinyi Chen, Zhizhan Chu, Heping Han, Eric Patterson, Qin Yu, Stephen Powles
Summary: This study revealed the complexity of the alpha-tubulin gene family in individuals/populations of the cross-pollinated weedy species L. rigidum, with multiple different transcripts and transcript sequences identified. A potential mutation was found that may confer dinitroaniline resistance in L. rigidum.
PEST MANAGEMENT SCIENCE
(2021)
Article
Multidisciplinary Sciences
Allison Ogren, Sneha Parmar, Soumya Mukherjee, Samuel J. Gonzalez, Melissa Plooster, Mark McClellan, Anirudh G. Mannava, Elliott Davidson, Trisha N. Davis, Melissa K. Gardner
Summary: Kinesin-14 motors play a role in controlling microtubule lengths by interacting with microtubule plus-ends and walking towards the minus-end. The binding of Kinesin-14 motors to microtubule plus-ends results in a decrease in microtubule lifetime and elongation, while inhibition of Kinesin-14 minus-end-directed motility leads to extended interactions and stabilization of microtubule plus-ends. This study demonstrates the importance of Kinesin-14 motors in regulating microtubule dynamics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Ivana Gasic
Summary: The genomes of higher eukaryotes contain a large tubulin gene superfamily with various isotypes. The expression and regulation of these isotypes in different cell types, as well as their impact on the biomechanical properties of the microtubule cytoskeleton, are still poorly understood. Recent studies shed light on the complex regulatory pathways involved in the expression and function of tubulin isotypes, particularly during development and in specialized cells. This review summarizes our current understanding of the regulation of tubulin isotype expression and its importance in building a customized microtubule network for cellular needs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Review
Cell Biology
Shih-Chieh Ti
Summary: This article provides an overview of the importance of tubulin in cellular structures and functions, and highlights the characteristics of purified α/β-tubulin heterodimers through in vitro experiments, revealing the regulatory mechanisms of microtubule dynamics and stability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Lei Diao, Wei Zheng, Qiaoyu Zhao, Mingyi Liu, Zhenglin Fu, Xu Zhang, Lan Bao, Yao Cong
Summary: This study purified recombinant tubulin heterodimers composed of different mouse α-tubulin isotypes and β-tubulin isotype and determined their structures. The results showed that the combination of different α-tubulin isotypes can affect microtubule structures, providing evidence for the tubulin code hypothesis.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2023)
Article
Crystallography
Noemi Sanchez-Castro, Martha Alicia Palomino-Ovando, Pushpendra Singh, Satyajit Sahu, Miller Toledo-Solano, Jocelyn Faubert, J. Eduardo Lugo, Anirban Bandyopadhyay, Kanad Ray
Summary: Researchers proposed a model suggesting that each tubulin dimer in microtubules can act as the period unit of a one-dimensional crystal, enabling signal transmission and processing through electromagnetic sensing.
Article
Cell Biology
Lei Diao, Ming-Yi Liu, Yin-Long Song, Xu Zhang, Xin Liang, Lan Bao
Summary: The study found that microtubules composed of different alpha-tubulin isotypes exhibit differences in growth rate and catastrophe frequency, largely attributed to variations in their C-terminal tails. Compared to alpha 1A/beta 2A microtubules, alpha 1C/beta 2A microtubules display higher growth rate and lower catastrophe frequency, which can be explained by the differences in their C-terminal tails.
JOURNAL OF MOLECULAR CELL BIOLOGY
(2021)
Review
Neurosciences
Graziella Cappelletti, Alessandra Maria Calogero, Chiara Rolando
Summary: This study discusses the importance of microtubule acetylation in controlling neuronal and glial function, as well as its role in neurodegenerative disorders. Research has found that microtubule acetylation is a key modification that controls intracellular transport and stability, potentially serving as a novel therapeutic intervention for diseases like Parkinson's.
NEUROSCIENCE LETTERS
(2021)
Article
Pharmacology & Pharmacy
Hong Tan, Huali Wang, Jinhu Ma, Hui Deng, Qinghua He, Qiang Chen, Qinglian Zhang
Summary: This study found that lactate dehydrogenase C (LDHC) is significantly expressed in lung cancer tissues, and overexpression of LDHC can promote tumor growth, while knock-down of LDHC can inhibit cancer cell proliferation. The crystal structure of human LDHC4 was determined and found to have a distinct conformation compared to LDHA4 and lactate dehydrogenase B4 (LDHB4). Additionally, (ethylamino) (oxo)acetic acid was shown to selectively inhibit LDHC4. These findings suggest that LDHC4 could be a potential target for anticancer drug discovery.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Multidisciplinary Sciences
Halina Mikolajek, Miriam Weckener, Z. Faidon Brotzakis, Jiandong Huo, Evmorfia Dalietou, Audrey Le Bas, Pietro Sormanni, Peter J. Harrison, Philip N. Ward, Steven Truong, Lucile Moynie, Daniel K. Clare, Maud Dumoux, Joshua Dormon, Chelsea Norman, Naveed Hussain, Vinod Vogirala, Raymond J. Owens, Michele Vendruscolo, James H. Naismith
Summary: This study generated nanobodies with different affinities using the receptor binding domain (RBD) of SARS-CoV-2 spike protein and a naive library. By analyzing the structure-activity relationship, it was found that higher conformational entropy losses were associated with tighter binding. Structural ensembles and conformational fluctuations were investigated to enhance the affinity of nanobodies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Charles J. Buchanan, Ben Gaunt, Peter J. Harrison, Yun Yang, Jiwei Liu, Aziz Khan, Andrew M. Giltrap, Audrey Le Bas, Philip N. Ward, Kapil Gupta, Maud Dumoux, Tiong Kit Tan, Lisa Schimaski, Sergio Daga, Nicola Picchiotti, Margherita Baldassarri, Elisa Benetti, Chiara Fallerini, Francesca Fava, Annarita Giliberti, Panagiotis Koukos, Matthew J. Davy, Abirami Lakshminarayanan, Xiaochao Xue, Georgios Papadakis, Lachlan P. Deimel, Virginia Casablancas-Antras, Timothy D. W. Claridge, Alexandre M. J. J. Bonvin, Quentin J. Sattentau, Simone Furini, Marco Gori, Jiandong Huo, Raymond J. Owens, Christiane Schaffitzel, Imre Berger, Alessandra Renieri, James H. Naismith, Andrew J. Baldwin, Benjamin G. Davis
Summary: This study utilizes universal saturation transfer analysis to reveal the interaction between the novel coronavirus and glycan compounds, and identifies protein mutations related to pathogenicity and zoonosis.
Article
Chemistry, Medicinal
Lucile Moynie, Francoise Hoegy, Stefan Milenkovic, Mathilde Munier, Aurelie Paulen, Veronique Gasser, Aline L. Faucon, Nicolas Zill, James H. Naismith, Matteo Ceccarelli, Isabelle J. Schalk, Gaetan L. A. Mislin
Summary: This study found that TCV can mimic the binding of ENT to the outer membrane transporter PfeA in Pseudomonas aeruginosa and can cross the bacterial outer membrane through this protein. This finding provides a promising vector for using the Trojan horse strategy against P. aeruginosa.
ACS INFECTIOUS DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Talya S. Levitz, Miriam Weckener, Ivan Fong, James H. Naismith, Catherine L. Drennan, Edward J. Brignole, Daniel K. Clare, Michele C. Darrow
Summary: The specimen preparation process is crucial for the success of cryo electron microscopy (cryoEM) structural studies. Traditional manual methods have limitations in speed and efficiency, while new automated technologies offer improved controllability and stability. As early users of the chameleon system, we share our experiences and lessons learned through case studies, providing recommendations for future users and the field of cryoEM specimen preparation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Wenbo Li, Georgina C. Girt, Ashish Radadiya, James J. P. Stewart, Nigel G. J. Richards, James H. Naismith
Summary: The biosynthetic enzyme ForT catalyzes the formation of a C-C bond and distinguishes between different molecules, providing insights for biocatalytic production. This study utilizes biophysical measurements, structural biology, and quantum chemical calculations to understand ForT-catalyzed C-C bond formation and conformational changes. The findings have implications for the production of novel anti-viral compounds.
Article
Multidisciplinary Sciences
Jie Cheng, Yamei Yu, Xingyu Wang, Xi Zheng, Ting Liu, Daojun Hu, Yongfeng Jin, Ying Lai, Tian-Min Fu, Qiang Chen
Summary: To form a functional neural circuit, neurons develop specific molecular features to distinguish self from non-self. Both the invertebrate Dscam family and the vertebrate Pcdh family play a role in determining synaptic specificity. A recently identified shortened Dscam (sDscam) in Chelicerata exhibits characteristics of both Dscam and Pcdh isoforms, representing an evolutionary transition. This study reveals the molecular details of sDscam self-recognition through trans and cis interactions, proposing a molecular zipper model for sDscam assemblies and cell-cell recognition.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Casper Berger, Maud Dumoux, Thomas Glen, Neville B. -y. Yee, John M. Mitchels, Zuzana Patakova, Michele C. Darrow, James H. Naismith, Michael Grange
Summary: Plasma-coupled ion sources are used to thin vitrified human cells, allowing for in situ structural biology studies inside cells and tissues.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Miriam Weckener, Laura S. Woodward, Bradley R. Clarke, Huanting Liu, Philip N. Ward, Audrey Le Bas, David Bhella, Chris Whitfield, James H. Naismith
Summary: The study reveals the regulatory mechanism of polysaccharide polymerization in Enterobacteriaceae bacteria. It demonstrates the formation of a complex between WzyE polymerase and WzzE polysaccharide co-polymerase, which together participate in the polymerization and regulation of polysaccharides. These findings provide important structural insights into the mechanism of polysaccharide chain length regulation in bacteria.
Article
Biology
Maud Dumoux, Thomas Glen, Jake L. R. Smith, Elaine M. L. Ho, Luis M. A. Perdigao, Avery Pennington, Sven Klumpe, Neville B. Y. Yee, David Andrew Farmer, Pui Y. A. Lai, William Bowles, Ron Kelley, Juergen M. Plitzko, Liang Wu, Mark Basham, Daniel K. Clare, C. Alistair Siebert, Michele C. Darrow, James H. Naismith, Michael Grange, Giulia Zanetti
Summary: Cryogenic plasma FIB/SEM overcomes challenges in imaging non-stained biological samples, producing high-quality images with automated workflows. This technique allows for three-dimensional imaging of bacteria, human cells, and tissue with resolutions typically ranging from 20-50 nm.
Article
Chemistry, Multidisciplinary
James M. Parkhurst, Adam D. Crawshaw, C. Alistair Siebert, Maud Dumoux, C. David Owen, Pedro Nunes, David Waterman, Thomas Glen, David I. Stuart, James H. Naismith, Gwyndaf Evans
Summary: Three-dimensional electron diffraction from nanocrystals of biological macromolecules requires the use of very small crystals, typically less than 300 nm-thick. Focused-ion-beam milling has been used to prepare thin samples for this purpose, but little work has been done to quantify the damage caused to delicate biological samples. This study analyzed the effect of plasma FIB milling on lysozyme crystals and compared argon and xenon plasmas with a gallium source. The results showed an upper bound and a lower bound for the depth of the milling damage layer.
Article
Biochemistry & Molecular Biology
Weizhi Chen, Rui Liu, Yamei Yu, Dongqing Wei, Qiang Chen, Qin Xu
Summary: This study uncovers the molecular mechanisms of cancer-causing mutations in DCLK1 by analyzing its crystal structure and performing molecular dynamics simulations. The disruption of the assembly of the autoinhibitory domain leads to exposure of a key residue in the kinase domain. The researchers conducted a screening process and evaluated the binding affinity of potential inhibitors to DCLK1.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Multidisciplinary Sciences
Anagha Madhusudanan, Christopher Iddon, Muge Cevik, James H. Naismith, Shaun Fitzgerald
Summary: The purpose of this review was to identify the effectiveness of environmental control non-pharmaceutical interventions (NPIs) in reducing transmission of SARS-CoV-2. A systematic review was conducted, and a total of 19 references provided evidence for the effectiveness of certain NPIs, such as ventilation and air cleaning devices. However, there was low confidence in the findings due to the low quality and certainty of the evidence.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES
(2023)
Article
Multidisciplinary Sciences
Dongmei Tang, Tingting Jia, Yongbo Luo, Biqin Mou, Jie Cheng, Shiqian Qi, Shaohua Yao, Zhaoming Su, Yamei Yu, Qiang Chen
Summary: In the spacer acquisition stage of CRISPR-Cas immunity, spacer orientation and protospacer adjacent motif (PAM) removal are important for functional spacer integration. Cas4 is involved in processing the prespacer and determining spacer orientation. Host 3'-5' DnaQ family exonucleases have been found to play a similar role in Cas4-lacking systems, but the details of their functions are still unclear.
Article
Biology
Audrey Le Bas, Halina Mikolajek, Jiandong Huo, Chelsea Norman, Joshua Dormon, James H. Naismith, Raymond J. Owens
Summary: The receptor binding domain (RBD) of the spike protein of SARS-CoV-2 interacts with angiotensin converting enzyme-2 (ACE-2) on epithelial cells, allowing the virus to enter the cell. However, llama-derived nanobodies (VHHs) can block this interaction and neutralize the virus. X-ray crystallography analysis of VHH-RBD complexes helps identify VHH epitopes and predict the effects of variant mutations. A workflow for expressing and purifying the proteins and screening conditions for high-quality crystals has been established.
