Editorial Material
Cell Biology
Bor Luen Tang
Summary: This article provides an editorial overview of the papers collected in this Special Issue on the Regulation and Function of Small GTPases 2.0.
Article
Biochemistry & Molecular Biology
Aaron M. N. Joiner, Ben P. Phillips, Kumar Yugandhar, Ethan J. Sanford, Marcus B. Smolka, Haiyuan Yu, Elizabeth A. Miller, J. Christopher Fromme
Summary: The study revealed the regulation of Rab1 activation by the TRAPPIII complex, with the Trs85 subunit serving as a membrane anchor for the entire complex via its amphipathic helix. These findings provide a structural understanding of Rab activation on organelle and vesicle membranes.
Article
Oncology
Xin Zhang, Liangliang Ren, Junhua Wu, Rongni Feng, Yunyang Chen, Ronggang Li, Meimei Wu, Mingzhu Zheng, Xing Gui Wu, Wanjun Luo, Hongle He, Yanming Huang, Miaoling Tang, Jun Li
Summary: ARHGEF37 is upregulated in HCC and associated with tumor invasiveness, pulmonary metastasis and poor prognosis. Overexpression of ARHGEF37 enhances HCC cell extravasation and metastasis by promoting cell adhesion and migration. ARHGEF37 activates Cdc42 to promote invadopodia formation in HCC cells, disrupting the interaction between endothelial cells and pericytes.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Immunology
Polly A. Machin, Anna-Karin E. Johnsson, Ellie J. Massey, Chiara Pantarelli, Stephen A. Chetwynd, Julia Y. Chu, Hanneke Okkenhaug, Anne Segonds-Pichon, Simon Walker, Angeliki Malliri, Yoshinori Fukui, Heidi C. E. Welch
Summary: Rac-GTPases and their Rac-GEF activators are essential for neutrophil-mediated host defence. Different Rac-GEFs activate distinct pools of Rac and regulate various neutrophil responses. Among them, Dock2 is the primary regulator, controlling neutrophil polarization, migration, and phagocytosis.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Xuehua Xu, Tian Jin
Summary: Chemotaxis is essential in leukocyte recruitment during inflammation. Adaptation is a strategy for cells to respond to chemoattractant gradients. Ras activation is the first step in GPCR signaling pathways, and Ras inhibitors regulate cell sensitivity.
FRONTIERS IN IMMUNOLOGY
(2022)
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
Urology & Nephrology
Jun Matsuda, Kana Asano-Matsuda, Thomas M. Kitzler, Tomoko Takano
Summary: Rho GTPases play a crucial role in regulating the actin cytoskeleton and are implicated in the pathogenesis of proteinuric glomerular diseases. These GTPases are primarily regulated by three families of proteins – GEFs, GAPs, and GDIs – with their upstream regulatory mechanisms largely unknown in podocytes. Further studies are needed to bridge the knowledge gap in the field.
KIDNEY INTERNATIONAL
(2021)
Article
Biochemistry & Molecular Biology
Pankaj Dipankar, Puneet Kumar, Pranita P. Sarangi
Summary: This study modelled the 3D structure of RhoG and evaluated the binding dynamics of ten Rac1 inhibitors to RhoG. The results suggest that Rac1 inhibitors may have the potential to be therapeutic agents for conditions involving dysregulation of RhoG.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Biochemistry & Molecular Biology
Saket R. Bagde, J. Christopher Fromme
Summary: Correct localization of Rab GTPases in cells is crucial for membrane trafficking. GEFs, such as TRAPP complexes TRAPPII and TRAPPIII, activate specific Rabs on organelle and vesicle membranes. The length of Rab C-terminal hypervariable domain (HVD) plays a critical role in substrate selection. Cryo-EM studies have provided insights into how TRAPP complexes identify and activate their substrates.
Article
Biochemistry & Molecular Biology
Mingxing Wang, Huan Feng, Peng Xu, Qiujin Xie, Jinpeng Gao, Yanzhang Wang, Xiaowei Zhang, Jun Yang, Jeremy D. Murray, Fengli Sun, Chunyan Wang, Ertao Wang, Nan Yu
Summary: The study identified the crucial roles of small GTPases and Nod factor receptor in root hair development and infection process in Medicago truncatula, regulating polar growth and deformation of root hairs through activation and interaction mechanisms.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2021)
Editorial Material
Biochemistry & Molecular Biology
Jianjun Duan, David G. Lambright
Summary: The article explores the structural basis for Sar1 activation by the Sec12 guanine nucleotide exchange factor during COPII vesicle biogenesis at the endoplasmic reticulum.
Article
Chemistry, Analytical
Jiarong Wang, Bo Wu, Youjia Zhang, Liang Ge, Junfeng Wang
Summary: In this study, a 1D F-19 NMR-based method was developed for rapid detection of GEF activity of sGTPases, by tracking the conformational changes of the Arf6 switch region. This strategy could potentially be applied to monitor the conformational change of Arf6 or other sGTPase and detect the activities of sGTPase regulatory proteins in physiology and pathology environments.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kiran S. Toti, John R. Jimah, Veronica Salmaso, Jenny E. Hinshaw, Kenneth A. Jacobson
Summary: This study investigates the impact of the North and South conformations of guanine nucleotides on dynamin-mediated membrane constriction and reveals that the activity of dynamin is dependent on the conformational state of the GTP nucleotide. However, natural dynamin structures predominantly exhibit the (S)-conformation, presenting a mismatch with the required (N) vs. (S) for GTP analogues in the dynamin-mediated process.
Article
Biology
Yasmin ElMaghloob, Begona Sot, Michael J. McIlwraith, Esther Garcia, Tamas Yelland, Shehab Ismail
Summary: The study demonstrates that BART acts as a bona fide co-GEF for ARL3, interacting with ARL3 and ARL13B to efficiently activate ARL3 and maintain its active state. This finding contributes to a better understanding of the role of ARL3 in regulating ciliary function.
Review
Cardiac & Cardiovascular Systems
Shane P. Comer
Summary: Platelet cytoskeletal reorganisation is important for platelet activation and thrombus formation. Rho GTPases play a critical role in this process, cycling between active and inactive states through the regulation of GAPs and GEFs. However, the functionality of Rho GTPase specific GAPs and GEFs in platelets is not well understood.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Medicine, General & Internal
Anna Jaskiewicz, Beata Pajak, Magdalena Labieniec-Watala, Clara De Palma, Arkadiusz Orzechowski
JOURNAL OF CLINICAL MEDICINE
(2019)
Review
Biochemistry & Molecular Biology
B. Pajak, E. Siwiak, M. Soltyka, A. Priebe, R. Zielinski, I. Fokt, M. Ziemniak, A. Jaskiewicz, R. Borowski, T. Domoradzki, W. Priebe
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Biochemistry & Molecular Biology
Marcin Ziemniak, Anna Zawadzka-Kazimierczuk, Sylwia Pawledzio, Maura Malinska, Maja Soltyka, Damian Trzybinski, Wiktor Kozminski, Stanislaw Skora, Rafal Zielinski, Izabela Fokt, Waldemar Priebe, Krzysztof Wozniak, Beata Pajak
Summary: The study reports the structural analysis of halogen-substituted derivatives of 2-DG, showing significant impact of halogens on crystal structure but not on conformation, and different intermolecular interactions. These findings provide a deeper understanding of the structural chemistry of halogen-substituted carbohydrates and their interactions with proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Tomasz Domoradzki, Piotr Grochowski, Anna Jaskiewicz, Beata Pajak
Summary: The study examines the correlation between prolonged exposure to ammunition-related chemicals and genomic instability predisposing to lung carcinogenesis in professional soldiers. Using modern molecular techniques, new somatic single nucleotide polymorphisms (SNPs) related to lung carcinogenesis were detected in soldiers with long-term exposure to ammunition-related toxic chemicals. This suggests that genetic analysis could be a valuable tool for monitoring genome instability and improving personnel safety in occupational settings.
JOURNAL OF APPLIED GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Beata Pajak, Ewelina Siwiak-Niedbalska, Anna Jaskiewicz, Maja Soltyka, Rafal Zielinski, Tomasz Domoradzki, Izabela Fokt, Stanislaw Skora, Waldemar Priebe
Summary: Research on 2-DG and its analogs has made significant progress in the past decade. Challenges in using 2-DG as a monotherapy have led researchers to focus on enhancing its bioavailability and exploring combinations with glycolysis inhibitors to synergistically eliminate cancer cells. The study presents promising evidence of synergistic cytotoxic effects in glioblastoma cells using 2-DG analogs combined with HDAC inhibitors.
Review
Biochemistry & Molecular Biology
Beata Pajak
Summary: Glioblastoma multiforme (GBM) is a deadly and complex brain cancer, and current standard treatment is limited. New chemotherapeutics are urgently needed.
Article
Biochemistry & Molecular Biology
Marcin Mielecki, Marcin Ziemniak, Magdalena Ozga, Radoslaw Borowski, Jaroslaw Antosik, Angelika Kaczynska, Beata Pajak
Summary: Protein aggregation is a common problem in industrial preparation and understanding its structure and function is crucial for the development of therapeutic proteins. This study analyzed the side products of a single-chain fusion cytotoxin and provided comprehensive insights into their molecular architecture and function.
Review
Biochemistry & Molecular Biology
Beata Pajak, Rafal Zielinski, John Tyler Manning, Stanislava Matejin, Slobodan Paessler, Izabela Fokt, Mark R. Emmett, Waldemar Priebe
Summary: Viral infection triggers metabolic changes in cells, particularly an upregulation of glycolysis. The glycolysis inhibitor 2-DG has been studied as an antiviral drug, but its pharmacokinetic properties limit its application.
Article
Biochemistry & Molecular Biology
Beata Pajak, Ewelina Siwiak-Niedbalska, Anna Jaskiewicz, Maja Soltyka, Tomasz Domoradzki
Summary: Glioblastoma multiforme (GBM) is a common primary malignant brain tumor with limited treatment options due to the blood-brain barrier (BBB). This study focuses on the design and synthesis of small-molecule anticancer agents that can penetrate the BBB, with a specific focus on the compound 2-deoxy-D-glucose (2-DG). A derivative of 2-DG called WP1234 has shown promising anticancer potential in vitro, inhibiting GBM cell viability, glycolysis, and histone deacetylases (HDAC) activity. Further studies are needed to evaluate its efficacy and safety in animal models and toxicology studies.
Article
Veterinary Sciences
Anna Jaskiewicz, Agnieszka Cholewiak-Goralczyk, Pawel Grudzinski, Lukasz Filipek, Beata Pajak, Katarzyna Pazdzior-Czapula, Iwona Otrocka-Domagala
Summary: This case study demonstrates the importance of close cooperation between oncologists and nutritionists in the successful treatment of cachectic patients with cancer.
MEDYCYNA WETERYNARYJNA-VETERINARY MEDICINE-SCIENCE AND PRACTICE
(2022)
Article
Chemistry, Multidisciplinary
Marcin Ziemniak, Sylwia Pawledzio, Anna Zawadzka-Kazmierczuk, Paulina M. Dominiak, Damian Trzybinski, Wiktor Kozminski, Rafal Zielinski, Izabela Fokt, Waldemar Priebe, Krzysztof Wozniak, Beata Pajak
Summary: The structural studies of two bromo-substituted derivatives of 2-deoxy-D-glucose revealed that bromine substitution has a significant impact on the crystal structure, leading to a layered supramolecular landscape containing hydrogen bonds involving the bromine atom. Periodic DFT calculations supported these findings, while NMR studies showed similarities in anomeric equilibria and pyranose ring puckering compared to 2-DG.
Review
Biochemistry & Molecular Biology
Anna Jaskiewicz, Tomasz Domoradzki, Beata Pajak
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
