Review
Biochemistry & Molecular Biology
Magdalena C. Vidalle, Bhavwanti Sheth, Antonietta Fazio, Maria Vittoria Marvi, Stefano Leto, Foteini-Dionysia Koufi, Irene Neri, Irene Casalin, Giulia Ramazzotti, Matilde Y. Follo, Stefano Ratti, Lucia Manzoli, Sonakshi Gehlot, Nullin Divecha, Roberta Fiume
Summary: Polyphosphoinositides (PPIns) are critical regulators of various cellular processes, despite their low concentration within the cell. These lipids are generated by the phosphorylation of phosphatidylinositol and are found in different subcellular compartments. In the nucleus, PPIns have been identified and their functions in nuclear signalling are still being elucidated. This review provides a current understanding of the localization, biogenesis, and physiological functions of different PPIns species in the nucleus.
Article
Biochemistry & Molecular Biology
Juyoun Yoo, Mark Dombrovski, Parmis Mirshahidi, Aljoscha Nern, Samuel A. Locascio, S. Lawrence Zipursky, Yerbol Z. Kurmangaliyev
Summary: Advances in brain connectomics have revealed the complexity of neural circuits. This study integrated the synapse-level connectome with developmental expression patterns and binding specificities of cell adhesion molecules to understand the wiring specificity in the Drosophila visual system. They found that specific receptor-ligand pairs play a crucial role in synaptic localization and connections.
Review
Oncology
Mitsunori Fukuda
Summary: Melanosomes, specialized organelles in melanocytes that produce and store melanin pigments, mature in stages and are transported to neighboring keratinocytes for pigment transfer. Rab GTPases play a crucial role in membrane trafficking processes important for skin and hair pigmentation.
PIGMENT CELL & MELANOMA RESEARCH
(2021)
Article
Cell Biology
David Bradley, Cristina Vieitez, Vinothini Rajeeve, Joel Selkrig, Pedro R. Cutillas, Pedro Beltrao
Summary: The study found that specificity-determining residues (SDRs) in protein kinases are mutated more frequently than catalytic residues, aiding in predicting kinase specificity. Kinase specificity is strongly conserved across evolution and can diverge through gene duplication.
Review
Biochemistry & Molecular Biology
Alazne Arrazola Sastre, Miriam Luque Montoro, Hadriano M. Lacerda, Francisco Llavero, Jose L. Zugaza
Summary: Rab and Arf GTPases play crucial roles in the pathogenesis and progression of neurodegenerative diseases, making them potential therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Si-Yi Li, Ming Shan, Zhao Zhai
Summary: Health climate is crucial in building construction projects, but has received limited attention in existing literature. This study aims to identify key determinants of health climate in such projects. Through a literature review and interviews with experienced experts, a hypothesis was developed connecting practitioners' perceptions of health climate and their health status. A questionnaire was then used for data collection, and the results were analyzed using partial least-squares structural equation modeling. The study found that health climate in building construction projects is positively related to practitioners' health status, and that employment involvement, management commitment, and supportive environment are the main determinants of health climate. This research contributes to the knowledge gap in construction health and provides valuable insights for authorities and practitioners to improve health in building construction projects.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Article
Green & Sustainable Science & Technology
Michal Stricik, Monika Conkova
Summary: The Slovak Republic is not meeting the waste economy targets in the long run, so changes are needed in the current municipal waste management system. The type of fee for municipal waste was identified as the most significant factor influencing waste sorting rates, with recommendations tailored to the needs of Slovak municipalities.
Article
Microbiology
Sung-Jae Cha, Xiang Yu, Brian D. Gregory, Yong Seok Lee, Tomoko Ishino, Robert O. Opoka, Chandy C. John, Marcelo Jacobs-Lorena
Summary: This study identifies activation and inhibition pathways leading to cerebral malaria (CM) and provides evidence from human specimens. The researchers found that liver infection by Plasmodium sporozoites can trigger immune responses that inhibit CM development. They also identified several early-stage prognostic biomarkers for CM, which have direct relevance to human CM.
Review
Microbiology
Serena Porcari, Nicolas Benech, Mireia Valles-Colomer, Nicola Segata, Antonio Gasbarrini, Giovanni Cammarota, Harry Sokol, Gianluca Ianiro
Summary: Fecal microbiota transplantation (FMT) has shown promising results in preventing recurrence of Clostridioides difficile infection, but its success in other diseases is limited. Factors influencing FMT success include donor and recipient-related factors, working protocols, and the degree of donor microbial engraftment. The use of advanced technologies for microbiome assessment and changes in the current vision of fecal transplants are expected to improve FMT outcomes. This review highlights key determinants of FMT success and strategies for integrating lab-based and clinical approaches.
CELL HOST & MICROBE
(2023)
Article
Biochemistry & Molecular Biology
Natalia Stach, Abdulkarim Karim, Przemyslaw Golik, Radoslaw Kitel, Katarzyna Pustelny, Natalia Gruba, Katarzyna Groborz, Urszula Jankowska, Sylwia Kedracka-Krok, Benedykt Wladyka, Marcin Drag, Adam Lesner, Grzegorz Dubin
Summary: By studying the substrate specificity and structure of SplF, it was found that the enzyme has a strict preference for long aliphatic sidechains at the P1 subsite and significant selectivity for aromatic residues at P3, with its crystal structure defining the structural basis of this substrate specificity. Comparisons with other Spl proteases suggest that the spl operon encodes a unique extracellular proteolytic system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Pharmacology & Pharmacy
Maria Pertusa, Jocelyn Solorza, Rodolfo Madrid
Summary: Cold thermoreceptor neurons detect temperature drops through sensitive molecular machinery in their peripheral free nerve endings. The main molecule responsible for this detection is the TRPM8 channel. Dysregulation of TRPM8 activity is linked to various diseases including cold hypersensitivity, migraine, dry-eye disease, overactive bladder, and cancer. A better understanding of TRPM8's activation and modulation mechanisms is necessary for developing targeted treatments. This review summarizes the current knowledge on TRPM8 and highlights the recent advancements in cryo-electron microscopy structures, providing insights for future drug design.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Cell Biology
Fan Bao, Peiqi Hao, Su An, Yang Yang, Ying Liu, Qian Hao, Mubashir Ejaz, Xiao-Xi Guo, Tian-Rui Xu
Summary: The phosphatidylinositol 3-kinase-Akt signaling pathway is crucial in regulating cell proliferation and apoptosis, with Akt kinase being a central player. Although Akt is frequently overexpressed in tumors, inhibiting it has significant clinical side effects, making it unsuitable for cancer treatment. Recent focus has shifted to Akt scaffold proteins as potential targets for cancer therapy, as they play a role in regulating Akt signaling specificity.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Xin Yong, Guowen Jia, Zhe Liu, Chunzhuang Zhou, Jiamin Yi, Li Chen, Lu Chen, Yuan Wang, Qingxiang Sun, Daniel D. Billadeau, Zhaoming Su, Da Jia
Summary: In this study, the structure of the Drosophila Mon1-Ccz1-RMC1 complex was determined using cryogenic-electron microscopy. RMC1 acts as a scaffolding subunit and binds to both Mon1 and Ccz1, explaining the binding specificity of the complex. The assembly of RMC1 with Mon1-Ccz1 is required for cellular RAB7A activation, autophagic functions, and organismal development in zebrafish.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Immunology
Rashmi Tippalagama, Leila Y. Chihab, Kendall Kearns, Sloan Lewis, Sudhasini Panda, Lisa Willemsen, Julie G. Burel, Cecilia Lindestam S. Arlehamn
Summary: TCR sequencing allows tracking of specific antigen-specific T cells and their clonal expansion, and has been widely used to study the role of these cells in different diseases.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Parasitology
Rachel Pool, Clara Romero-Rubira, Juan Antonio Raga, Mercedes Fernandez, Francisco Javier Aznar
Summary: The study found that lungworm infection patterns varied among different cetacean species, with certain hosts having higher infection levels. Larger nematodes were mainly found in host species with the highest parasite burden.
PARASITES & VECTORS
(2021)
Article
Biochemistry & Molecular Biology
Sophie Vieweg, Katie Mulholland, Bastian Braeuning, Nitin Kachariya, Yu-Chiang Lai, Rachel Toth, Pawan Kishor Singh, Ilaria Volpi, Michael Sattler, Michael Groll, Aymelt Itzen, Miratul M. K. Muqit
BIOCHEMICAL JOURNAL
(2020)
Article
Microbiology
A. Leoni Swart, Bernhard Steiner, Laura Gomez-Valero, Sabina Schuetz, Mandy Hannemann, Petra Janning, Michael Irminger, Eva Rothmeier, Carmen Buchrieser, Aymelt Itzen, Vikram Govind Panse, Hubert Hilbi
Article
Multidisciplinary Sciences
Stefan Ernst, Felix Ecker, Marietta S. Kaspers, Philipp Ochtrop, Christian Hedberg, Michael Groll, Aymelt Itzen
Article
Multidisciplinary Sciences
Jiqing Du, Marie-Kristin von Wrisberg, Burak Gulen, Matthias Stahl, Christian Pett, Christian Hedberg, Kathrin Lang, Sabine Schneider, Aymelt Itzen
Summary: Legionella pneumophila infects eukaryotic cells by modifying the activity of Rab1 protein through DrrA/SidM protein secretion. A chemical approach was used to study the interaction between Rab1 and DrrA, revealing a non-conventional Rab-binding site. This interaction allosterically activates DrrA, providing insights into Legionella infection mechanism.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Sergey Savitskiy, Rudolf Wachtel, Danial Pourjafar-Dehkordi, Hyun-Seo Kang, Vanessa Trauschke, Don C. Lamb, Michael Sattler, Martin Zacharias, Aymelt Itzen
Summary: The proteolysis of Rab32 by Salmonella typhimurium affects various biochemical and structural properties of the GTPase in diverse ways, demonstrating a localized increase in conformational flexibility and a disruption in the interaction with downstream effectors.
Review
Biochemical Research Methods
Joel Fauser, Aymelt Itzen, Burak Gulen
Summary: This review discusses the limitations of structural characterization of macromolecular assemblies due to transient interactions and highlights the importance of covalently tethering interacting proteins using specific chemical tools. Various protein engineering techniques and biochemical methodologies have been employed to stabilize macromolecular complexes for structural investigation, enabling advancements in diverse scientific fields.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Joel Fauser, Burak Gulen, Vivian Pogenberg, Christian Pett, Danial Pourjafar-Dehkordi, Christoph Krisp, Dorothea Hoepfner, Gesa Koenig, Hartmut Schlueter, Matthias J. Feige, Martin Zacharias, Christian Hedberg, Aymelt Itzen
Summary: The study reveals that FICD regulates the domain-docked conformation of BiP through specific binding of TPR motifs to the conserved hydrophobic linker, affecting the AMPylation and deAMPylation of BiP. Furthermore, the AMPylation and deAMPylation of BiP are not directly regulated by the presence of unfolded proteins.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sergey Savitskiy, Aymelt Itzen
Summary: The study demonstrates that Salmonella SopD and SopD2 act as RabGAPs, inactivating Rab signaling pathways through their unique substrate specificity and catalytic efficiencies. The mutagenesis studies provide insights into the key residues involved in the conversion of active to inactive GTPases for Rab proteins.
BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
(2021)
Review
Biochemistry & Molecular Biology
Burak Gulen, Aymelt Itzen
Summary: AMPylation is a post-translational modification catalyzed by AMP-transfering enzymes, playing a major role in hijacking host signaling during infection and modulating cellular functions. The mechanism of AMPylation requires further investigation.
TRENDS IN MICROBIOLOGY
(2022)
Correction
Multidisciplinary Sciences
Dorothea Hoepfner, Joel Fauser, Marietta S. Kaspers, Christian Pett, Christian Hedberg, Aymelt Itzen
Article
Chemistry, Multidisciplinary
Mohammad Akbarzadeh, Jana Flegel, Sumersing Patil, Erchang Shang, Rishikesh Narayan, Marcel Buchholzer, Neda S. Kazemein Jasemi, Michael Grigalunas, Adrian Krzyzanowski, Daniel Abegg, Anton Shuster, Marco Potowski, Hacer Karatas, George Karageorgis, Niloufar Mosaddeghzadeh, Mia-Lisa Zischinsky, Christian Merten, Christopher Golz, Lucas Brieger, Carsten Strohmann, Andrey P. Antonchick, Petra Janning, Alexander Adibekian, Roger S. Goody, Mohammad Reza Ahmadian, Slava Ziegler, Herbert Waldmann
Summary: This study combines biological relevance and fragment-based design to discover novel compounds with potential new biological targets. Through synthesizing pseudo-natural products, a first small-molecule ligand of RHOGDI1 was identified.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Amrita Rai, Anurag K. Singh, Nathalie Bleimling, Guido Posern, Ingrid R. Vetter, Roger S. Goody
Summary: Rep15 is an effector that interacts with the GTPase Rab15. Here, the authors show that Rep15 also interacts with Rab3 paralogs and Rab34, present crystal structures of Rep15:Rab complexes and find that Rep15 depletion in glioblastoma cells decreases proliferation and mobility.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Matthias Frese, Philip Saumer, Yizhi Yuan, Doreen Herzog, Dorothea Hoepfner, Aymelt Itzen, Andreas Marx
Summary: Diadenosine polyphosphates (Ap(n)As) are non-canonical nucleotides that increase in cellular concentrations during stress and act as alarmones to regulate homeostasis. This study investigates the role of Ap(n)As in protein AMPylation, a post-translational modification that transfers adenosine monophosphate (AMP) to proteins. The findings demonstrate that Ap(4)A can be efficiently utilized for AMPylation by FICD and identify potential new AMPylation targets. Interestingly, the study suggests that the AMPylation targets of FICD may vary depending on the nucleotide cosubstrate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
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
Biology
Lisa Goebel, Tonia Kirschner, Sandra Koska, Amrita Rai, Petra Janning, Stefano Maffini, Helge Vatheuer, Paul Czodrowski, Roger S. Goody, Matthias P. Mueller, Daniel Rauh
Summary: In this study, we developed nucleotide-based covalent inhibitors for the oncogenic mutant KRasG13C, which has been difficult to target in the past. These inhibitors showed promising properties and successfully locked KRasG13C in a crystal structure. Importantly, the modified KRasG13C protein with these inhibitors was unable to undergo nucleotide exchange and induce oncogenic signaling in cells, suggesting the potential use of nucleotide-based inhibitors for KRasG13C-driven cancer.
