Article
Multidisciplinary Sciences
Hugo van den Hoek, Nikolai Klena, Mareike A. Jordan, Gonzalo Alvarez Viar, Ricardo D. Righetto, Miroslava Schaffer, Philipp S. Erdmann, William Wan, Stefan Geimer, Jurgen M. Plitzko, Wolfgang Baumeister, Gaia Pigino, Virginie Hamel, Paul Guichard, Benjamin D. Engel
Summary: The cilium is an organelle similar to an antenna that plays various important roles in cellular functions. The base of the cilium has a selective barrier that controls the entry of large cargo proteins required for ciliary assembly and maintenance. This study used in situ cryo-electron tomography and ultrastructure expansion microscopy to reveal the native structures of the ciliary base and the assembly process of IFT trains.
Article
Biochemistry & Molecular Biology
Adrian Pascal Nievergelt, Ilia Zykov, Dennis Diener, Aditya Chhatre, Tim-Oliver Buchholz, Markus Delling, Stefan Diez, Florian Jug, Ludek Stepanek, Gaia Pigino
Summary: Cilia or eukaryotic flagella are microtubule-based organelles involved in intraflagellar transport (IFT), a system that moves cargo required for their assembly and maintenance. Previous studies suggested the presence of specific machinery at the ciliary tip to control IFT, but this research shows that IFT can be induced at arbitrary distances from the tip, independent of calcium ions.
Article
Biochemistry & Molecular Biology
Shengping Huang, Larissa L. Dougherty, Prachee Avasthi
Summary: Kinesin-2, composed of KIF3A/3B and KAP3, plays vital roles in cell division and intraorganellar transport, and is highly conserved across species. RanGTP regulates ciliary trafficking of KAP3 and the ARM6-9 region is necessary for both nuclear translocation and ciliary base targeting of KAP3. The precise control of RanGTP levels is crucial for cilium formation and maintenance, with implications for the understanding of nuclear import mechanisms in ciliary import.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Mahmoud R. Fassad, Nisreen Rumman, Katrin Junger, Mitali P. Patel, James Thompson, Patricia Goggin, Marius Ueffing, Tina Beyer, Karsten Boldt, Jane S. Lucas, Hannah M. Mitchison
Summary: Ciliopathies are genetic disorders caused by defective cilia, manifesting with various clinical features. A homozygous 3-kb intragenic IFT74 deletion was detected in two affected siblings, leading to cilia structural abnormalities, skeletal dysplasia, and primary ciliary dyskinesia (PCD). This hypomorphic mutation results in residual protein function and a combined phenotype of skeletal ciliopathy and defective motile cilia.
HUMAN MOLECULAR GENETICS
(2023)
Article
Polymer Science
Matthew F. I. Rix, Kyle Collins, Samuel J. Higgs, Eleanor M. Dodd, Simon J. Coles, Nathaniel M. Bingham, Peter J. Roth
Summary: This study demonstrates the various reactions of thionolactone DBT and its ability to introduce a degradable backbone. Additionally, through XRD structure analysis and DFT modeling, the higher reactivity of DBT is explained by its stabilization of the intermediate radical, increased ring strain, and better reinitiating efficiency.
Article
Chemistry, Multidisciplinary
Maosheng Li, Hongyu Li, Xiaoyong Zhang, Xianhong Wang, Youhua Tao
Summary: Exploiting non-covalent interactions to catalyze ionic polymerizations is still in its early stages. A recent study demonstrated non-covalent anion-binding catalysis for living cationic polymerization of vinyl ethers. This study further investigates the structure-reactivity relationships and roles of anion-binding interactions in the catalytic process. The findings provide insights into the mechanism of anion-binding catalytic polymerization and offer guidance for future catalyst design.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Cell Biology
Takuya Kobayashi, Yamato Ishida, Tomoaki Hirano, Yohei Katoh, Kazuhisa Nakayama
Summary: The study demonstrates the important role of IFT-A's IFT144-IFT122 and IFT-B's IFT88-IFT52 in mediating ciliary transport through their cooperation, facilitating the entry of GPCRs and retrograde trafficking of the IFT machinery from the ciliary tip.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Multidisciplinary Sciences
Tatsuro Noguchi, Kentaro Nakamura, Yuuki Satoda, Yohei Katoh, Kazuhisa Nakayama
Summary: CCRK interacts with BROMI to regulate ciliary Hedgehog signaling and both proteins cooperate in regulating ciliary protein trafficking.
Review
Urology & Nephrology
Ailis L. Moran, Laura Louzao-Martinez, Dominic P. Norris, Dorien J. M. Peters, Oliver E. Blacque
Summary: Primary cilia serve as cell surface antennae, coordinating cellular responses to sensory inputs and signaling molecules that regulate development and homeostasis. The compartmentalized structure of cilia, along with active transport pathways and gating mechanisms, plays a crucial role in maintaining its unique molecular composition and signaling environment. Understanding the major compartmentalizing pathways at the cilium has provided insights into ciliary disease and associated renal disorders.
NATURE REVIEWS NEPHROLOGY
(2023)
Article
Ophthalmology
Mariia Dvoriashyna, Alexander J. E. Foss, Eamonn A. Gaffney, Rodolfo Repetto
Summary: This article presents a mathematical model for predicting the production rate and composition of aqueous humor (AH) in the eye. The model provides insights into the controlling parameters and potential manipulation strategies for regulating aqueous production. Key factors impacting aqueous production rate are identified, including cell membrane permeability, ion transporters, and carbonic anhydrase.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2022)
Article
Engineering, Environmental
Kangying Guo, Zhining Wang, Jingwen Pan, Beibei Liu, Yan Wang, Qinyan Yue, Yue Gao, Baoyu Gao
Summary: In this study, a series of Al-Ti gels with different Ti/TEA, Ti/H2O, and Ti/Al ratios were prepared by sol-gel process. The interaction mechanism between Al and Ti was explored, and the most efficient Al-Ti gel was applied to lake water treatment. The results showed that Al-Ti gel had higher removal efficiency for organic matter compared to Ti gel, providing theoretical guidance for the study of the interaction mechanism between Al and Ti in composite coagulants and actual water treatment.
Article
Engineering, Environmental
Kangying Guo, Zhining Wang, Jingwen Pan, Beibei Liu, Yan Wang, Qinyan Yue, Yue Gao, Baoyu Gao
Summary: A series of Al-Ti gels with different ratios were prepared in this study, and their interaction mechanism was confirmed through FTIR and XPS analysis. The selected Al-Ti gel showed a UV254 removal efficiency of over 60% in lake water treatment.
Article
Cell Biology
Mareike A. Jordan, Gaia Pigino
Summary: The intraflagellar transport (IFT) system is a crucial molecular machine used by cells to assemble and maintain the cilium, shuttling structural components and signaling receptors within the organelle. IFT trains, composed of IFT-A and IFT-B adaptor protein complexes, are powered by kinesin-2 and IFT-dynein motors for bidirectional movement along microtubules.
JOURNAL OF CELL SCIENCE
(2021)
Article
Engineering, Chemical
Haigang Liu, Beibei Liu, Yue Gao, Yan Wang, Qinyan Yue, Kangying Guo, Baoyu Gao
Summary: A series of polymerized ferric titanium coagulants (PFTC) with different basicity and Ti/Fe molar ratio were prepared to remove natural organic matters (NOM) causing membrane fouling in water treatment process. The effects of basicity and Ti/Fe molar ratio on the structure of PFTC hydrolysates were explored through infrared and X-ray spectroscopy. The coagulation results showed that PFTC with low basicity and moderate Ti/Fe molar ratio efficiently removed UV254, DOC, and turbidity.
SEPARATION AND PURIFICATION TECHNOLOGY
(2023)
Article
Multidisciplinary Sciences
Zhisen Yang, Jing Xia, Jingjing Hong, Chenxi Zhang, Hong Wei, Wei Ying, Chunqiao Sun, Lianghanxiao Sun, Yanbo Mao, Yongxiang Gao, Shutang Tan, Jiri Friml, Dianfan Li, Xin Liu, Linfeng Sun
Summary: This study reports different conformational structures of Arabidopsis thaliana PIN1, revealing the substrate recognition and transport mechanisms of PIN proteins. These findings are of great significance for understanding the directional auxin transport process in plant development.
Article
Biochemistry & Molecular Biology
Miao Gui, Meisheng Ma, Erica Sze-Tu, Xiangli Wang, Fujiet Koh, Ellen D. Zhong, Bonnie Berger, Joseph H. Davis, Susan K. Dutcher, Rui Zhang, Alan Brown
Summary: Cryo-EM structures of radial spokes and nexin-dynein regulatory complex (N-DRC) attached to doublet microtubules isolated from Chlamydomonas reinhardtii provide a model for mechanoregulation of motile cilia.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Miao Gui, Xiangli Wang, Susan K. Dutcher, Alan Brown, Rui Zhang
Summary: The authors used cryo-EM to build atomic models of the central apparatus of motile cilia from Chlamydomonas reinhardtii and identified 48 different CA-associated proteins. They revealed mechanisms for asymmetric and periodic protein binding to microtubules and discovered a novel class of microtubule inner protein. These structures provide a foundation for further understanding ciliary motility and related diseases.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Hematology
Jacob R. Anderson, Jing Li, Timothy A. Springer, Alan Brown
Summary: This study reveals the structural features and formation mechanism of von Willebrand factor (VWF) tubules using electron cryomicroscopy (cryo-EM), providing a foundation for further understanding of the mutations causing von Willebrand disease (VWD).
Editorial Material
Biochemistry & Molecular Biology
Alan Brown, Franca Fraternali
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Miao Gui, Jacob T. Croft, Davide Zabeo, Vajradhar Acharya, Justin M. Kollman, Thomas Burgoyne, Johanna L. Hoog, Alan Brown
Summary: This study used single-particle cryo-electron microscopy methods to investigate the structure of human ciliary microtubules. Two types of microtubules were studied, and atomic models were built. It was discovered that SPACA9 is a polyspecific microtubule inner protein capable of binding different types of microtubules.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Manuel F. Juette, Jordan D. Carelli, Emily J. Rundlet, Alan Brown, Sichen Shao, Angelica Ferguson, Michael R. Wasserman, Mikael Holm, Jack Taunton, Scott C. Blanchard
Summary: This study determines how the natural products didemnin B and ternatin-4 inhibit translational elongation on mammalian ribosomes using single-molecule fluorescence imaging and cryogenic electron microscopy. These natural products trap the elongation factor eEF1A in an intermediate state of aa-tRNA selection, preventing translation. The study also reveals that didemnin B and ternatin-4 have different effects on the dynamics of aa-tRNA selection, explaining the observed differences in their inhibition efficacies and physiological impacts.
Article
Biochemistry & Molecular Biology
Miguel Ricardo Leung, Jianwei Zeng, Xiangli Wang, Marc C. Roelofs, Wei Huang, Riccardo Zenezini Chiozzi, Johannes F. Hevler, Albert J. R. Heck, Susan K. Dutcher, Alan Brown, Rui Zhang, Tzviya Zeev-Ben-Mordehai
Summary: Sperm motility is crucial for successful reproduction, but the ornamentation of axonemal microtubules and its support for motility in different fertilization environments are unclear. This study investigates native axonemal doublet microtubules (DMTs) in sea urchin and bovine sperm and identifies over 60 proteins decorating DMTs, including those linked to infertility. Through analyzing DMTs across species and cell types, the study defines core microtubule inner proteins (MIPs) and examines the evolution of the tektin bundle. Furthermore, a testis-specific serine/threonine kinase that connects DMTs to outer dense fibers in mammalian sperm is identified. The study provides structural insights into sperm evolution, motility, and dysfunction at a molecular level.
Article
Biochemistry & Molecular Biology
Lunni Zhou, Haobin Liu, Siyu Liu, Xiaoyu Yang, Yue Dong, Yun Pan, Zhuang Xiao, Beihong Zheng, Yan Sun, Pengyu Huang, Xixi Zhang, Jin Hu, Rui Sun, Shan Feng, Yi Zhu, Mingxi Liu, Miao Gui, Jianping Wu
Summary: Using cryo-EM and AI-based modeling, the structures of mouse and human sperm DMTs were determined and an atomic model of the mouse sperm DMT was built. Analysis revealed 47 DMT-associated proteins, including 45 MIPs. The study also identified variants in 10 distinct MIPs associated with asthenozoospermia, expanding the genetic spectrum of male infertility.
Article
Multidisciplinary Sciences
Travis Walton, Miao Gui, Simona Velkova, Mahmoud R. Fassad, Robert A. Hirst, Eric Haarman, Christopher O'Callaghan, Mathieu Bottier, Thomas Burgoyne, Hannah M. Mitchison, Alan Brown
Summary: The recent research achievements have determined the atomic models of the 96-nm modular repeats of axonemes, revealing the conservation and specialization of axonemes and the mechanisms that regulate ciliary motility. The structures of respiratory-cilia doublet microtubules from individuals with PCD have shown how the loss of individual docking factors can selectively eradicate periodically repeating structures.