Article
Biochemistry & Molecular Biology
Biao Yuan, Athina G. Portaliou, Rinky Parakra, Jochem H. Smit, Jiri Wald, Yichen Li, Bindu Srinivasu, Maria S. Loos, Harveer Singh Dhupar, Dirk Fahrenkamp, Charalampos G. Kalodimos, Franck Duong van Hoa, Thorben Cordes, Spyridoula Karamanou, Thomas C. Marlovits, Anastassios Economou
Summary: Type III protein secretion is common in Gram-negative pathogens, with SctV forming peripheral oligomeric clusters in EPEC and serving as a key receptor for different chaperone/exported protein pairs. The dynamic motions of SctV protomers, modulated by chaperones and ATPase, may allosterically affect the secretion process.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Jyoti M. Gurung, Ayad A. A. Amer, Shiyun Chen, Andreas Diepold, Matthew S. Francis
Summary: YscX, an important component of the Yersinia type III secretion system, remains poorly understood in terms of its function and mode of action. This study identified an N-terminal secretion domain in YscX that promotes its own secretion and contains essential information for its function. The secretion permissiveness of YscX is closely related to the assembly of an operational secretion system.
MOLECULAR MICROBIOLOGY
(2022)
Review
Microbiology
Meenakumari Muthuramalingam, Sean K. Whittier, Wendy L. Picking, William D. Picking
Summary: Shigella, a human-restricted pathogen causing bacillary dysentery, primarily relies on a type III secretion system (T3SS) consisting of multiple components and proteins for its virulence. Studying the T3SS injectisome in Shigella and related systems helps to understand its pathogenic mechanisms and develop prevention strategies.
Article
Biotechnology & Applied Microbiology
Qianqian Huang, Kui Zhang, Yu Li, Fei Gan, Xiao-Feng Tang, Bing Tang
Summary: Vpr-like proteases are widely distributed in bacteria and fungi and play important roles in processing lantibiotics, degrading collagen, keratin, and fibrin, and contributing to the pathogenesis of microbes. This study investigates a novel Vpr-like protease (BTV) from thermophilic bacterium Brevibacillus sp. WF146, revealing insights into its maturation and oligomerization mechanisms. The results show that hetero-catalytic maturation of BTV is more efficient than autocatalytic maturation, and the fibronectin type III domains mediate the dimerization of mature BTV while the N-terminal propeptide inhibits the dimerization of the proform.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jonas Weidenhausen, Juergen Kopp, Laura Armbruster, Markus Wirtz, Karine Lapouge, Irmgard Sinning
Summary: The majority of eukaryotic proteins undergo N-terminal acetylation, with Naa50 playing a crucial role in plant development and stress response regulation. The high-resolution crystal structures of AtNaa50 provide insights into its substrate specificity and enzymatic parameters, highlighting differences between species and serving as a basis for further studies.
Article
Immunology
Shoichi Tachiyama, Ryan Skaar, Yunjie Chang, Brittany L. Carroll, Meenakumari Muthuramalingam, Sean K. Whittier, Michael L. Barta, Wendy L. Picking, Jun Liu, William D. Picking
Summary: Shigella flexneri, the causative agent of bacillary dysentery, utilizes a type III secretion system as its primary virulence factor to inject effector proteins into host cells. The cytoplasmic sorting platform of the injectisome, specifically the Spa33 pods, plays a critical role in substrate selection and secretion energizing. Through biophysical analyses, a model of Spa33 heterotrimers within the SP pods is proposed, suggesting how two distinct complexes come together to form complete pod structures during the recruitment of T3SS secretion substrates.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Alireza Felegary, Shahram Nazarian, Emad Kordbacheh, Javad Fathi, Mohamad Ebrahim Minae
Summary: This study evaluated the antibody response and protection of a recombinant chimeric protein against Shigella, finding that the protein produced in E. coli could be a promising candidate for vaccine development against Shigella. The chimeric protein showed high antibody response and neutralization ability against the bacterial toxin, providing significant protection in immunized mice against both S. flexneri and S.dysentery.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Chemistry, Medicinal
Omur Guven, Belgin Sever, Faika Basoglu-Unal, Abdulilah Ece, Hiroshi Tateishi, Ryoko Koga, Mohamed O. Radwan, Nefise Demir, Mustafa Can, Mutlu Dilsiz Aytemir, Jun-ichiro Inoue, Masami Otsuka, Mikako Fujita, Halilibrahim Ciftci, Hasan Demirci
Summary: TRAF6 is a protein with important biological functions, and its structural studies play a crucial role in the development of new therapeutic drugs. By analyzing the structure and mechanism of TRAF6, we have identified new compounds that interact with its key regions and demonstrated their favorable pharmacokinetic properties, making them potential TRAF6 inhibitors in the future.
Article
Infectious Diseases
Raphael Sierocki, Bakhos Jneid, Maria Lucia Orsini Delgado, Marc Plaisance, Bernard Maillere, Herve Nozach, Stephanie Simon
Summary: Salmonella and Shigella are significant pathogens causing enteric infections, particularly in developing countries, and the development of broadly protective therapies is essential due to the emergence of antibiotic-resistant strains. By targeting needle tip proteins SipD for Salmonella and IpaD for Shigella, a monoclonal antibody was identified to have good cross-protection prophylactic efficacy, providing potential for the development of cross-protective therapeutic agents.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Article
Microbiology
Yoon-Suk Kang, James E. Kirby
Summary: Gram-negative pathogens rely on T4SS for infection, but there is a lack of ideal reporters to study T4SS function. Researchers have developed a novel reporter system using NLuc fusions to address this limitation.
MICROBIOLOGY SPECTRUM
(2023)
Review
Microbiology
Elizabeth A. Rucks
Summary: Type III secretion systems (T3SS) are utilized by Gram-negative pathogens to deliver effector proteins into target eukaryotic cells for manipulating cell functions and enhancing pathogenesis. This review will discuss the history, biochemical characterization, and function of chlamydial T3SS, as well as the use of heterologous/surrogate models for studying it. The review will also cover the history of chlamydial effectors and recent advances in the field.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2023)
Article
Multidisciplinary Sciences
Eduardo Soto, Jorge E. Galan, Marfa Lara-Tejero
Summary: In this study, an extensive in vivo cross-linking strategy aided by structure modeling was used to investigate the sorting platform complex of type III secretion systems. The assembly process of this bacterial structure was mapped using identified cross-links as signatures for pairwise intersubunit interactions and systematic genetic deletions. Insights generated by this study could be used for the rational development of antivirulence strategies against medically important bacterial pathogens.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Microbiology
Poyin Chen, Brian C. Russo, Jeffrey K. Duncan-Lowey, Natasha Bitar, Keith T. Egger, Marcia B. Goldberg
Summary: Shigella species use a type 3 secretion system to deliver virulence factors into host cells through a pore formed by IpaB and IpaC proteins. IpaB plays a crucial role in forming and organizing the pore channel, allowing for efficient delivery of virulence proteins into host cells during infection. This study provides insights into the molecular mechanisms underlying the function of the Shigella translocon during infection.
Article
Microbiology
Navoun Silue, Francois-Xavier Campbell-Valois
Summary: Shigella utilizes a Type III Secretion Apparatus to translocate proteins into host cells, including two newly discovered chromosomal genes - icaR and icaT, which can also be activated by MxiE and IpgC. These genes are secreted by T3SA independently of chaperones, and have orthologs in various E. coli strains belonging mainly to phylogroups A, B1, D, and E.
Article
Biochemistry & Molecular Biology
Ivana Malcova, Ladislav Bumba, Filip Uljanic, Darya Kuzmenko, Jana Nedomova, Jana Kamanova
Summary: Research has shown that the BteA effector protein binds to negatively charged membrane phospholipids through its lipid raft targeting domain. The binding constants for different lipids were determined, and it was found that phosphatidylinositol 4,5-bisphosphate, phosphatidic acid, and phosphatidylserine were required for targeting the BteA effector to the plasma membrane of yeast cells. Additionally, electrostatic and hydrophobic interactions were involved in the membrane association of the effector protein.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Microbiology
Rory Hennell James, Justin C. Deme, Andreas Kjaer, Felicity Alcock, Augustinas Silale, Frederic Lauber, Steven Johnson, Ben C. Berks, Susan M. Lea
Summary: The study reveals the internal structure and working mechanism of the gliding motility/type 9 protein secretion system motor, demonstrating that proton flow results in rotation of the GldM/PorM dimer inside the intra-membrane ring to drive processes at the bacterial outer membrane.
NATURE MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Susan K. Vester, Rebecca L. Beavil, Steven Lynham, Andrew J. Beavil, Deborah S. Cunninghame Graham, James M. McDonnell, Timothy J. Vyse
Summary: The study identified nucleolin as a cell surface receptor of C1QTNF4, with interaction mediated by the second C1q-like domain of C1QTNF4 and the C terminus of nucleolin. C1QTNF4 primarily targets monocytes and B cells, actively internalizing upon cell binding. The findings contribute to a better understanding of C1QTNF4's role in the healthy immune system and its association with the development of systemic lupus erythematosus.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Veronica F. Ilkow, Anna M. Davies, Balvinder Dhaliwal, Andrew J. Beavil, Brian J. Sutton, James M. McDonnell
Summary: This study provides insights into the evolutionary differences between murine and human CD23, as well as highlighting some of the functional variances between CD23 in different species.
Article
Biochemical Research Methods
Caroline Pollard, Mark Hudson, James M. McDonnell, Paul G. Royall, Kim Wolff
Summary: A specific POCT for detecting MDMA in latent fingerprints has not been explored. The study aimed to design a sensitive POCT using SPR and LFA technology. By identifying a high-affinity antibody binding pair and testing titrations of fluorescently labelled antibody and antigen concentrations to allow clear distinction between negative and positive outcomes, a sensitive LFA screening tool was successfully designed. The tool showed better performance compared to a lower threshold of 40 pg/10 mu l.
DRUG TESTING AND ANALYSIS
(2022)
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
Biotechnology & Applied Microbiology
William N. D. Gao, Chen Gao, Janet E. Deane, David C. J. Carpentier, Geoffrey L. Smith, Stephen C. Graham
Summary: Researchers have solved the crystal structure of the vaccinia virus E2 protein, revealing its unique folded domains. Recent advances in deep learning methods have greatly improved the accuracy of predicting protein structures, which has significant implications for structural virology and molecular virology.
JOURNAL OF GENERAL VIROLOGY
(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
Biology
Rachel J. Harding, Justin C. Deme, Johannes F. Hevler, Sem Tamara, Alexander Lemak, Jeffrey P. Cantle, Magdalena M. Szewczyk, Nola Begeja, Siobhan Goss, Xiaobing Zuo, Peter Loppnau, Alma Seitova, Ashley Hutchinson, Lixin Fan, Ray Truant, Matthieu Schapira, Jeffrey B. Carroll, Albert J. R. Heck, Susan M. Lea, Cheryl H. Arrowsmith
Summary: The study provides a biophysical and structural characterization of the complex between huntingtin (HTT) and HAP40 proteins, demonstrating the coupling of HAP40 abundance with HTT and greater conformational variety in the mutant HTT's exon 1 compared to the wildtype, which is crucial for future drug discovery studies targeting Huntington's disease.
COMMUNICATIONS BIOLOGY
(2021)
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.
Article
Biochemistry & Molecular Biology
Irmgard Sinning, Melanie A. McDowell
Summary: Tail-anchored (TA) proteins are biologically important membrane proteins. Recent studies using cryo-electron microscopy have provided new insights into the molecular mechanisms of TA protein biogenesis and removal.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tomasz H. Benedyk, Viv Connor, Eve R. Caroe, Maria Shamin, Dmitri I. Svergun, Janet E. Deane, Cy M. Jeffries, Colin M. Crump, Stephen C. Graham
Summary: Herpes simplex virus-1 (HSV-1) alters cellular membrane lipid composition during infection. This study demonstrates that a virus-encoded protein, pUL21, promotes the conversion of ceramide (Cer) to sphingomyelin (SM) by activating CERT. The study also reveals the importance of specific protein-protein interactions in HSV-1 mediated sphingolipid metabolism.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biology
Iain M. Hay, Katie E. Mulholland, Tiffany Lai, Stephen C. Graham, Hayley J. Sharpe, Janet E. Deane
Summary: The research demonstrates that PTPRK selectively dephosphorylates substrates by binding to Afadin, indicating that PTP substrate specificity can be determined by protein-protein interactions. This phosphorylation-independent interaction, mediated through binding to a non-catalytic domain, highlights the potential function of receptor PTPs as intracellular scaffolds.
Review
Immunology
J. M. McDonnell, B. Dhaliwal, B. J. Sutton, H. J. Gould
Summary: The evolution of IgE in mammals provided an additional layer of immune protection at body surfaces for rapid and local response against environmental antigens. The IgE immune response includes expulsive and inflammatory forces against local antigen stimulation, but it may also cause tissue damage and allergic disease. Two well-known IgE receptors, FceRI and CD23, mediate IgE activities. Unlike other antibody receptors, CD23 also regulates IgE expression to maintain IgE homeostasis. Recent research has revealed previously unknown mechanisms for regulation of IgE and IgE complexes, such as the dynamic structure of IgE and its allosteric modulation capacity.
ANNUAL REVIEW OF IMMUNOLOGY
(2023)
Editorial Material
Biochemistry & Molecular Biology
Susan M. Lea, Pamela A. Williams
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Prasun Kundu, Deboki Naskar, Shannon J. Mckie, Sheena Dass, Usheer Kanjee, Viola Introini, Marcelo U. Ferreira, Pietro Cicuta, Manoj Duraisingh, Janet E. Deane, Julian C. Rayner
Summary: This study reveals the molecular function of the Plasmodium TRAg family, which is encoded by a multi-gene family and significantly expanded in P. vivax and related parasites. The TRAgs are expressed on the merozoite surface, with one specific TRAg binding to red blood cells, particularly reticulocytes. Structural analysis shows that the TRAg family has a conserved three-helical bundle that resembles lipid-binding BAR domains involved in membrane remodelling. Biochemical assays confirm the TRAg's ability to bind to sulfatide, a glycosphingolipid present in the outer leaflet of plasma membranes. Moreover, deletion of the putative orthologue in P. knowlesi affects invasion in reticulocytes, indicating the importance of TRAg during this essential process.
NATURE COMMUNICATIONS
(2023)