Article
Immunology
Ines P. Monteiro, Sofia Sousa, Vitor Borges, Paulo Goncalves, Joao Paulo Gomes, Luis Jaime Mota, Irina S. Franco
Summary: Two novel effectors, VFX05045 and VFX10045, of Legionella pneumophila were identified and their subcellular localizations were determined. Furthermore, the essential residues for nuclear targeting of VFX10045 were identified.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Marietta S. Kaspers, Vivian Pogenberg, Christian Pett, Stefan Ernst, Felix Ecker, Philipp Ochtrop, Michael Groll, Christian Hedberg, Aymelt Itzen
Summary: In this study, the authors uncover the mechanism and substrate recognition of Legionella effector Lem3, which removes a phosphocholine moiety from the human protein Rab1 during infection. They present the crystal structure of the stabilised Lem3:Rab1b complex, revealing the catalytic mechanism and substrate recognition of PPM phosphatases shaped Lem3. This research is of significant importance for understanding bacterial pathogenesis and protein substrate recognition.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
J. Allombert, C. Jaboulay, C. Michard, C. Andrea, X. Charpentier, A. Vianney, P. Doublet
Summary: The Legionella pneumophila Icm/Dot T4SS can translocate a large number of effectors, and research has found that their delivery is controlled by specific timing to effectively manipulate host cells. The timed delivery of effectors depends not only on chaperone protein interactions but also involves cyclic-di-GMP signaling.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ivy Y. W. Chung, Lei Li, Oleg Tyurin, Alla Gagarinova, Raissa Wibawa, Pengfei Li, Elizabeth L. Hartland, Miroslaw Cygler
Summary: Legionella pneumophila is an intracellular pathogen that causes Legionnaire's disease in humans. It enters host cells through phagocytosis and affects host cellular processes by secreting over 300 effector proteins. RavA, a L. pneumophila effector, displays unique structural characteristics and localizes to the Golgi apparatus and plasma membrane in human cells.
Article
Biochemistry & Molecular Biology
Sun Cheol Park, So Yeon Cho, Tae Hee Kim, Kyung Yeol Ko, Wan Seok Song, Seung Goo Kang, Geun-Shik Lee, Sung-il Yoon
Summary: LegK7 is an atypical kinase that activates through interaction with the host MOB1 protein without the need for phosphorylation. Upon binding with MOB1, LegK7 undergoes a structural reshaping that allows it to adopt a closed conformation compatible with ATP binding.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Dominik A. Machtens, Jonas M. Willerding, Susanne Eschenburg, Thomas F. Reubold
Summary: The Gram-negative bacterium Legionella pneumophila is an accidental human pathogen that causes Legionellosis. During infection, L. pneumophila injects more than 300 effector proteins into the host cell to modify the intracellular environment and create a stable compartment for proliferation. The effector protein SidI inhibits host translation by interacting with eEF1A and may have a toxic effect due to its glycosyltransferase domain.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Immunology
Alix McCloskey, Kayla Perri, TaoTao Chen, Aidong Han, Zhao-Qing Luo
Summary: Legionella pneumophila uses effectors and metaeffectors to manipulate host processes and regulate its virulence through specific mechanisms such as protein modification and direct binding.
MICROBES AND INFECTION
(2021)
Article
Multidisciplinary Sciences
Tao-Tao Chen, Yanling Lin, Shijun Zhang, Shuxin Liu, Lei Song, Wenhong Zhong, Zhao-Qing Luo, Aidong Han
Summary: The intracellular bacterial pathogen Legionella pneumophila hijacks host vesicular transport factor p115 to localize its effector protein LegA15 in host lipid droplets (LDs) and causes fragmentation of host Golgi apparatus. LegA15 is an atypical GTPase that modulates host LD homeostasis through its GTPase activity.
Review
Microbiology
Ashley M. Joseph, Stephanie R. Shames
Summary: This review discusses the function of metaeffectors in Legionella pneumophila, which regulate other effectors essential for pathogen replication. While there are at least a dozen known metaeffectors in L. pneumophila, their exact mechanisms of promoting virulence remain largely unknown. The review also highlights challenges in identifying and understanding the contribution of metaeffectors to bacterial pathogenesis.
Article
Biochemistry & Molecular Biology
Miles H. Black, Adam Osinski, Gina J. Park, Marcin Gradowski, Kelly A. Servage, Krzysztof Pawlowski, Vincent S. Tagliabracci
Summary: ADP-ribosyltransferases (ARTs) are a widespread superfamily of enzymes commonly used by bacteria in pathogenic strategies. Legionella pneumophila has a diverse set of 330 translocated effectors, but the ART effectors influencing this bacteria have not been well defined. The discovery of Legionella ADP-Ribosyltransferase 1 (Lart1) targeting a host metabolic enzyme during infection represents a novel mechanism of pathogenicity for this bacterium.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kevin Voth, Shivani Pasricha, Ivy Yeuk Wah Chung, Rachelia R. Wibawa, Engku Nuraishah Huda E. Zainudin, Elizabeth L. Hartland, Miroslaw Cygler
Summary: Legionella pneumophila is a Gram-negative intracellular pathogen causing Legionnaires' disease, using a secretion system and effector proteins to colonize host cells. MavL may play a role in cell signaling by binding ADP-ribose, and interacts with the mammalian ubiquitin-conjugating enzyme.
Article
Multidisciplinary Sciences
Yunjia Shi, Hongtao Liu, Kelong Ma, Zhao-Qing Luo, Jiazhang Qiu
Summary: Legionella organisms are environmental bacteria that cause Legionnaires' disease. A study characterized an effector protein, RavZ, in L. longbeachae, the second leading cause of Legionella infections. RavZ inhibits autophagy signaling in host cells challenged with L. pneumophila and L. longbeachae, indicating functional redundancy between RavZ(LLO) and RavZ(LP). RavZ(LLO) also reduces cellular levels of polyubiquitinated and polyneddylated proteins. RavZ(LLO) plays a role in the regulation of polyubiquitinated species on the Legionella-containing vacuole during L. longbeachae infection.
Review
Immunology
Tshegofatso Ngwaga, Deepika Chauhan, Stephanie R. Shames
Summary: The article discusses the immune responses mediated by effector proteins in Gram-negative bacterial pathogens and the potential future of developing new drugs using effector proteins.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yu Guo, Dan Zhou, Hui Zhang, Nan-Nan Zhang, Xiaoyu Qi, Xiaofang Chen, Qi Chen, Jing Li, Honghua Ge, Yan-Bin Teng
Summary: This study investigates the structural characteristics of MapA in HAPs and its substrate recognition mechanism. By analyzing the binding of the complex with inhibitors, a new substrate binding mode is revealed.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yongshan Gao, Xiaowen Yang, Lan Hua, Min Wang, Qing Ge, Weiqiang Wang, Na Wang, Jinming Ma, Honghua Ge
Summary: In this study, the crystal structure of Legionella pneumophila aspartate aminotransferase (Lpg0070) and its functionality were investigated. The results revealed the crucial role of the N-terminal arm in enzyme activity.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Gabriel Waksman
Article
Biochemistry & Molecular Biology
Andrew M. Hartley, Natalya Lukoyanova, Yunyi Zhang, Alfredo Cabrera-Orefice, Susanne Arnold, Brigitte Meunier, Nikos Pinotsis, Amandine Marechal
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Stephan Lange, Nikos Pinotsis, Irina Agarkova, Elisabeth Ehler
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2020)
Article
Multidisciplinary Sciences
Andrew M. Hartley, Brigitte Meunier, Nikos Pinotsis, Amandine Marechal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Amit Meir, Kevin Mace, Natalya Lukoyanova, David Chetrit, Manuela K. Hospenthal, Adam Redzej, Craig Roy, Gabriel Waksman
NATURE COMMUNICATIONS
(2020)
Article
Multidisciplinary Sciences
Nikos Pinotsis, Karolina Zielinska, Mrigya Babuta, Joan L. Arolas, Julius Kostan, Muhammad Bashir Khan, Claudia Schreiner, Anita Salmazo, Luciano Ciccarelli, Martin Puchinger, Eirini A. Gkougkoulia, Euripedes de Almeida Ribeiro, Thomas C. Marlovits, Alok Bhattacharya, Kristina Djinovic-Carugo
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
James R. Sayer, Karin Wallden, Hans Koss, Helen Allan, Tina Daviter, Paul J. Gane, Gabriel Waksman, Alethea B. Tabor
Summary: H. pylori infections are linked to gastric ulcers and cancers, with challenges in current therapies due to antibiotic resistance. Studies focus on inhibiting HP0525 and exploring potential bivalent inhibitors. Through various methods and structural details of subunit interactions, the aim is to improve selectivity and develop these compounds as tools for probing the assembly of the HP0525 hexamer.
JOURNAL OF PEPTIDE SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Kevin Mace, Amit Meir, Natalya Lukoyanova, Luying Liu, David Chetrit, Manuela K. Hospenthal, Craig R. Roy, Gabriel Waksman
Summary: The study revealed the significance of DotY and DotZ in maintaining the stability and localization of T4CC, with these two proteins showing a codependent relationship. Additionally, DotY and DotZ were found to regulate the dynamic movement of the IcmSW module.
MOLECULAR MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shumeng Ma, Shymaa Damfo, Jiaqi Lou, Nikos Pinotsis, Matthew W. Bowler, Shozeb Haider, Frank Kozielski
Summary: The regular reappearance of coronavirus outbreaks has caused significant consequences globally. The ongoing pandemic caused by SARS-CoV-2 has highlighted the need for safe and effective antiviral drugs. The study identified fragment hits against the N-terminal domain of SARS-CoV-2 nsp1 and determined ligand-binding sites, providing a starting point for the development of more potent nsp1-targeting inhibitors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Christopher A. Waudby, Saul Alvarez-Teijeiro, E. Josue Ruiz, Simon Suppinger, Nikos Pinotsis, Paul R. Brown, Axel Behrens, John Christodoulou, Anastasia Mylona
Summary: Protein phosphorylation regulates cellular signaling, and the phosphorylation of c-JUN at multiple sites controls various functional states in signal response.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Amit Meir, Kevin Mace, Yogesh Vegunta, Sunanda M. Williams, Gabriel Waksman
Summary: This review provides an update on recent advances in substrate recruitment and delivery by recruitment platforms associated with Type III, IV, and VI secretion systems in gram-negative bacteria.
TRENDS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shumeng Ma, Vitaliy Mykhaylyk, Matthew W. Bowler, Nikos Pinotsis, Frank Kozielski
Summary: The authors propose a method to identify binding orientations of 2-dimensional fragments containing sulphur or chloro substituents using tunable beamlines. They successfully validate previously reported conformations and determine the positions of sulphur and chlorine in fragments bound to their protein target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Cell Biology
Ekaterina P. Lamber, Pascale Guicheney, Nikos Pinotsis
Summary: Transversal structural elements in cross-striated muscles, such as the M-band or the Z-disc, play important roles in anchoring and mechanically stabilizing the sarcomere. Specifically, the M-band acts as a mechanical and signaling hub during contraction and impairment of its function can lead to disease and death. Research on the M-band architecture has focused on the assembly and interactions of three major filamentous proteins, including myomesin-2 and myomesin-3, but limited information is available. Recent studies have linked the myomesin protein family, especially myomesin-2, to serious cardiovascular diseases, highlighting their importance in muscle function and disease.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Adam Redzej, Marta Ukleja, Sarah Connery, Martina Trokter, Catarina Felisberto-Rodrigues, Adam Cryar, Konstantinos Thalassinos, Richard D. Hayward, Elena V. Orlova, Gabriel Waksman