Article
Biochemistry & Molecular Biology
Michael Blaber
Summary: Beta-trefoil proteins exhibit approximate C-3 rotational symmetry, with conserved beta-strands and divergent turn regions. Different functional families of beta-trefoils can potentially be identified by their unique turn patterns. Such analyses provide insights into the evolution and de novo protein design of beta-trefoil proteins.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biology
Frederic Angles, Chao Wang, William E. Balch
Summary: Spatial covariance analysis shows how each residue in the critical fold region of chloride channel CFTR, defective in cystic fibrosis patients, contributes to CFTR's export from the endoplasmic reticulum and function in the cell.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Safoura Salar, Nicolas E. E. Ball, Hiba Baaziz, Jay C. C. Nix, Richard C. C. Sobe, K. Karl Compton, Igor B. B. Zhulin, Anne M. M. Brown, Birgit E. E. Scharf, Florian D. D. Schubot
Summary: Chemotaxis is a fundamental process for bacteria to seek nutrients and avoid harmful chemicals. In the symbiotic soil bacterium Sinorhizobium meliloti, the chemotaxis system is also crucial in its interaction with its legume host. In this study, the crystal structure of the periplasmic domain of McpZ (McpZPD) was determined, revealing a novel fold consisting of three concatenated four-helix bundle modules. Molecular dynamics calculations suggest that ligand binding induces conformational changes and specific movements in the protein structure, which closely resemble those observed in other ligand-bound MCP-LBDs.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Orthopedics
Jay R. Ebert, Peter Edwards, Brendan Joss, Peter Annear, Ross Radic, Peter D'Alessandro
Summary: This study found limb symmetry differences at specific points despite high LSIs in peak knee extensor and flexor torque. Gender, meniscal surgery, and ACLR on dominant or non-dominant limb did not significantly affect limb differences.
Article
Sport Sciences
Jay R. Ebert, Luke Du Preez, Bonnie Furzer, Peter Edwards, Brendan Joss
Summary: The study found significant differences in LSIs across hop tests, with LSIs of single leg hop, 6m timed hop, triple hop, and triple crossover hop all greater than 90%, while LSIs of single medial, single lateral hop, single countermovement jump, and timed speedy hop were all less than 90%. The LSI for the single countermovement jump was significantly lower than all other hop tests.
INTERNATIONAL JOURNAL OF SPORTS PHYSICAL THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Oliver Adams, Justin C. Deme, Joanne L. Parker, Philip W. Fowler, Susan M. Lea, Simon Newstead
Summary: The structure analysis of Mtb MmpL3 can help us understand the mechanism of drug resistance mutations, revealing the positioning of resistance variants at the drug binding site, and also highlighting a potential alternative route to resistance within the periplasmic domain.
Article
Multidisciplinary Sciences
Joanne L. Parker, Justin C. Deme, Zhiyi Wu, Gabriel Kuteyi, Jiandong Huo, Raymond J. Owens, Philip C. Biggin, Susan M. Lea, Simon Newstead
Summary: The proton-coupled solute carriers PepT1 and PepT2 in the SLC15 family are crucial for acquiring dietary nitrogen and have extreme substrate promiscuity. Recent studies on their structure and function provide insights into their potential applications in drug development.
Article
Microbiology
Jessica E. Martyn, Giulia Pilla, Sarah Hollingshead, Kristoffer S. Winther, Susan Lea, Gareth McVicker, Christoph M. Tang
Summary: Shigella sonnei is a major cause of bacillary dysentery and becoming more concerning due to multidrug resistance. It spontaneously becomes avirulent during laboratory growth through loss of its virulence plasmid (pINV). This study investigated the mechanisms of avirulence in S. sonnei and found that it mainly results from pINV loss. The limited repertoire and amino acid sequences of plasmid-encoded toxin-antitoxin (TA) systems contribute to plasmid loss in S. sonnei. These findings provide new insights for reducing plasmid loss in S. sonnei and facilitating research and vaccine development.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Multidisciplinary Sciences
Katharina Braunger, Jiyoon Ahn, Matthijs M. Jore, Steven Johnson, Terence T. L. Tang, Dennis V. Pedersen, Gregers R. Andersen, Susan M. Lea
Summary: The authors report the identification and characterisation of a species-specific properdin inhibitor CirpA derived from tick saliva, opening avenues for future therapeutic approaches.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Dusan Zivkovic, Angelique Sanchez Dafun, Thomas Menneteau, Adrien Schahl, Sandrine Lise, Christine Kervarrec, Ana Toste Rego, Paula C. A. da Fonseca, Matthieu Chavent, Charles Pineau, Odile Burlet-Schiltz, Julien Marcoux, Marie-Pierre Bousquet
Summary: During spermatogenesis, the proteasome plays a crucial role in regulating cell division processes. The s20S proteasome becomes highly active during meiosis, mainly through 19S activation and PA200 binding. The proteasome population shifts from c20S to s20S during differentiation, and s20S interacts with components of the meiotic synaptonemal complex. In vitro, s20S shows higher trypsin- and chymotrypsin-like activities and displays structural differences between alpha 4 and alpha 4s.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Rory Hennell James, Justin C. Deme, Alicia Hunter, Ben C. Berks, Susan M. Lea
Summary: Gliding motility and protein secretion through the type IX secretion system (T9SS) are two specific features of the Bacteroidetes. These processes are energized by the GldLM motor complex, which converts the proton motive force into mechanical work. The structures of the GldLM motor complex from different Bacteroidetes species reveal a conserved architecture, but with species-specific differences at the N terminus of GldL. This study enhances our understanding of bacterial ion-driven motors and their role in T9SS and gliding motility.
Editorial Material
Biochemistry & Molecular Biology
Susan M. Lea, Pamela A. Williams
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Nisha Pillay, Laura Mariotti, Mariola Zaleska, Oviya Inian, Matthew Jessop, Sam Hibbs, Ambroise Desfosses, Paul C. R. Hopkins, Catherine M. Templeton, Fabienne Beuron, Edward P. Morris, Sebastian Guettler
Summary: This research reveals the structure of the active unit filament of tankyrase and shows how its catalytic and non-catalytic functions are controlled by polymerization. The cryo-electron microscopy reconstruction provides detailed insights into the interactions between the SAM domain and the catalytic domain, as well as the role of head-to-head and tail-to-tail interactions at the active site.
Article
Cell Biology
Xinrui Huang, Iratxe Torre, Michele Chiappi, Zhan Yin, Anupama Vydyanath, Shuangyi Cao, Oliver Raschdorf, Morgan Beeby, Bonnie Quigley, Pieter P. de Tombe, Jun Liu, Edward P. Morris, Pradeep K. Luther
Summary: Myosin binding protein C (MyBP-C) is a rod-shaped protein composed of 10 or 11 immunoglobulin- or fibronectin-like domains that binds to the thick filament in vertebrate cardiac muscle. It regulates contraction in a phosphorylation-dependent manner and its 3D organization in the sarcomere may provide insights into its function. Cryo-electron tomography revealed the fine structure of MyBP-C in relaxed rat cardiac muscle, showing its connection to actin and suggesting potential interactions with myosin heads. The finding of a distinct structure at Stripe 4 may have broader implications in cardiac and skeletal muscles.
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
(2023)
Article
Oncology
Aaron Javitt, Merav D. Shmueli, Matthias P. Kramer, Aleksandra A. Kolodziejczyk, Ivan J. Cohen, Lihi Radomir, Daoud Sheban, Iris Kamer, Kevin Litchfield, Elizabeta Bab-Dinitz, Oranit Zadok, Vanessa Neiens, Adi Ulman, Hila Wolf-Levy, Avital Eisenberg-Lerner, Assaf Kacen, Michal Alon, Ana Toste Rego, Elvira Stacher-Priehse, Michael Lindner, Ina Koch, Jair Bar, Charles Swanton, Yardena Samuels, Yishai Levin, Paula C. A. da Fonseca, Eran Elinav, Nir Friedman, Silke Meiners, Yifat Merbl
Summary: Immunotherapy has significantly improved cancer treatment, but the reasons behind resistance in some patients are still not well understood. The composition of cellular proteasomes has been found to influence tumor-immune interactions and the tumor microenvironment, modulating the response to immunotherapy. By studying the degradation patterns in patient-derived non-small-cell lung carcinoma samples, the upregulation of proteasome regulator PSME4 was observed in tumors, leading to changes in proteasome activity, reduced antigenic diversity, and lack of response to immunotherapy. Therefore, precision oncology should focus on examining and targeting the heterogeneity and function of proteasome composition across different cancer types.
Biographical-Item
Cell Biology
Edward P. Morris, Carlo Knupp, Pradeep K. Luther
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
(2023)
Editorial Material
Cell Biology
Pradeep K. Luther, Edward P. Morris, David A. D. Parry, Kenneth A. Taylor
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
(2023)
Article
Cell Biology
Marston Bradshaw, John M. Squire, Edward Morris, Georgia Atkinson, Rebecca Richardson, Jon Lees, Massimo Caputo, Giulia M. Bigotti, Danielle M. Paul
Summary: This study used cryo-EM to investigate the three-dimensional structure of zebrafish cardiac thin and actin filaments, and found that they have the same fundamental organization as human reconstituted thin filaments. Zebrafish, as a model organism for human disease research, have similar genes and disease-causing genes to humans, making them suitable for studying human diseases.
JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY
(2023)
Article
Biochemistry & Molecular Biology
Ioanna Deni, Barbara H. Stokes, Kurt E. Ward, Kate J. Fairhurst, Charisse Flerida A. Pasaje, Tomas Yeo, Shirin Akbar, Heekuk Park, Ryan Muir, Daniella S. Bick, Wenhu Zhan, Hao Zhang, Yi Jing Liu, Caroline L. Ng, Laura A. Kirkman, Jehad Almaliti, Alexandra E. Gould, Maelle Duffey, Anthony J. O'Donoghue, Anne-Catrin Uhlemann, Jacquin C. Niles, Paula C. A. da Fonseca, William H. Gerwick, Gang Lin, Matthew Bogyo, David A. Fidock
Summary: This study found that vinyl sulfone inhibitors are effective against artemisinin-resistant parasites and do not readily develop resistance. Additionally, resistance to one inhibitor can increase sensitivity to other types of inhibitors. These findings suggest that dual targeting of different proteasome subunits using covalent inhibitors may be a potential strategy for restoring artemisinin activity and combating drug-resistant malaria spread.
CELL CHEMICAL BIOLOGY
(2023)
Meeting Abstract
Biophysics
Pedro Carvalho, Yoel Klug, Justin Deme, Susan Lea
BIOPHYSICAL JOURNAL
(2021)