Article
Biochemistry & Molecular Biology
Sonali Tayal, Venugopal Bhatia, Tanya Mehrotra, Sonika Bhatnagar
Summary: This study curated experimental host-pathogen and host-host protein-protein interactions, annotated the domains and motifs of these proteins, and proposed the concept of mimicry pairs. The results were organized in a web-based resource called ImitateDB, which allows for easy querying of a large number of identified mimicry pairs in interacting host and pathogen proteins.
Review
Microbiology
Vera Vozandychova, Pavla Stojkova, Kamil Hercik, Pavel Rehulka, Jiri Stulik
Summary: Ubiquitination, similar to phosphorylation and acetylation, plays a crucial role in regulating various cell processes. Understanding how pathogens manipulate host ubiquitination processes is important for vaccine development and disease treatment. Pathogenic bacteria encode effector proteins targeting the host ubiquitin machinery to disrupt host defense processes.
Article
Biochemistry & Molecular Biology
Jordi Gomez Borrego, Marc Torrent Burgas
Summary: Adhesion and colonization of host cells by pathogenic bacteria rely on protein-protein interactions (PPIs). This study developed a filtering process to obtain a reliable list of domains and motifs participating in PPIs between bacteria and human cells. Structural analysis revealed that human proteins involved in these interactions are rich in alpha helix and disordered regions. The most significant domain-domain interactions were validated, but verifying domain-motif interactions was more challenging. Post-translational modifications, especially phosphorylation, also play a role in these interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Asahiro Morishita, Kyoko Oura, Tomoko Tadokoro, Koji Fujita, Joji Tani, Tsutomu Masaki
Summary: The liver is a non-immunological organ involved in metabolic activities, nutrient storage, and detoxification. Resident immune cells in the liver drive immunological reactions and certain microRNAs are associated with the immune response to pathogens, although the exact mechanism of miRNA interference in these interactions remains unclear.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Hitoshi Iuchi, Junna Kawasaki, Kento Kubo, Tsukasa Fukunaga, Koki Hokao, Gentaro Yokoyama, Akiko Ichinose, Kanta Suga, Michiaki Hamada
Summary: The COVID-19 pandemic has revealed the limitations of medical and research institutions in managing emerging infectious diseases. Predicting virus-host interactions through host range prediction and protein-protein interaction prediction can enhance our understanding of infectious diseases. Although multiple algorithms have been developed for this purpose, there are still challenges that need to be addressed. Despite the difficulties, bioinformatics can play a significant role in advancing research on infectious diseases and human health.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Cell Biology
Ana Katic, Dario Huesler, Francois Letourneur, Hubert Hilbi
Summary: This article introduces the haploid social amoeba Dictyostelium discoideum as a model organism for studying vesicle trafficking, motility and migration, cell division, and other biological processes, and discusses the crucial role of Dynamin superfamily proteins (DSPs) in these processes. Major progress has been made in elucidating the function and structure of mammalian and D. discoideum DSPs, and the potential of using the genetically tractable amoeba to further study the role of DSPs in cell and infection biology is emphasized.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Fisheries
Nur Fathiah Rosilan, Khor Waiho, Hanafiah Fazhan, Yeong Yik Sung, Nor Hafizah Zakaria, Nor Afiqah-Aleng, Zeti-Azura Mohamed-Hussein
Summary: Protein-protein interactions play a key role in cell physiology and can be used to explore the pathobiology of infectious diseases in shrimp. Through bibliometric analysis, this study provides insights into research trends in this field and highlights the importance of HP-PPI and approaches for identifying pathogens.
FISH & SHELLFISH IMMUNOLOGY
(2023)
Article
Genetics & Heredity
Guoqing Zhao, Pengpai Li, Xu Qiao, Xianhua Han, Zhi-Ping Liu
Summary: lncRNA-protein interactions play essential roles in cellular processes, but experimental methods are time-consuming and expensive. This study proposes a computational method called LncPNet that predicts potential interactions by embedding an lncRNA-protein network. Experimental results show promising performance and superior prediction compared to other methods.
FRONTIERS IN GENETICS
(2022)
Review
Physiology
Mian Muhammad Awais, Muhammad Shakeel, Jingchen Sun
Summary: miRNAs are small non-coding RNAs of about 22 nucleotides that have been reported to regulate gene expression at the posttranscriptional level, involved in various biological processes such as immunity, development, metabolism, and host-pathogen interactions. Both cellular and viral miRNAs may play vital roles in host-pathogen interactions, with viral infections altering host miRNA expression profiles.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Immunology
Hannah P. Berguson, Lauren W. Caulfield, Michael S. Price
Summary: This review summarizes the current knowledge on the mutants in carbon metabolism and their effect on the host immune response of Cryptococcus neoformans. Understanding these critical interactions will provide fresh perspectives on potential treatments and the natural history of cryptococcal disease.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Javier Macho Rendon, Rocio Rebollido-Rios, Marc Torrent Burgas
Summary: Protein-protein interactions play important roles in cellular processes. To address the limited knowledge of host-pathogen interactomes, we developed HPIPred, a numerical encoding-based host-pathogen PPI prediction tool. Through screening the entire proteomes of Homo sapiens and Pseudomonas aeruginosa PAO1, we generated a highly connected network topology of host-pathogen interactome using HPIPred.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Review
Microbiology
Wassim Daher, Virginia Pichler, Jona Karam, Olivier Neyrolles, Laurent Kremer
Summary: This review summarizes the complexity of interactions between mycobacterial ligands and host receptors during infection and pathogenesis. It highlights the recognition of pathogen-associated molecular patterns by phagocytic pattern recognition receptors as the first step of the infection process. It discusses the downstream effects of receptor-mediated pathways in promoting mycobacterial survival or activating host immune defenses, and the potential of mycobacterial surface molecules as therapeutic targets, diagnostic markers, or vaccine candidates.
FEMS MICROBIOLOGY REVIEWS
(2023)
Article
Biology
Sravan Kumar Miryala, Sudha Ramaiah
Summary: This study investigated the molecular interactions between host cellular components and F. tularensis genes, revealing pathways associated with pathogen offensive strategies and key genes crucial for invading host defense systems. The identified pathways are involved in adapting to host stress conditions and could be important for developing new therapeutic interventions against tularemia.
COMPUTATIONAL BIOLOGY AND CHEMISTRY
(2022)
Article
Immunology
Yang Fang, Yi Yang, Chengcheng Liu
Summary: This study proposes a new method to extract features from phylogenetic profiles for predicting pathogen-host interactions (PHIs). The performance of this approach is better than structure-based and machine learning-based methods, and combining phylogenetic profile features with structure-based methods can be applied to explore PHI and discover new unknown biological relationships.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Review
Immunology
Amanda Brosius Lutz, Salwan Al-Nasity, Boris W. Kramer, Martin Mueller
Summary: Chorioamnionitis, inflammation of the chorion and/or amnion during pregnancy, has significant implications for mother, fetus, and newborn; animal models play a crucial role in deepening understanding of the disease mechanisms; various animal models provide unique opportunities to study the inflammatory response and its consequences in chorioamnionitis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ryan C. Maloney, Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
Summary: Interactions between MEK1, B-Raf, and KSR1 are crucial for Ras/Raf/MEK/ERK signaling. Molecular dynamics simulations reveal that the proline-rich loop of MEK1 is essential for the phosphorylation of MEK1 activation loop. In the inactive B-Raf/MEK1 complex, the collapsed A-loop of B-Raf interacts with the P-rich loop and A-loop of MEK1, preventing phosphorylation. In the active B-Raf/MEK1 complex, the P-rich loop moves with the extended A-loop of B-Raf, leading to increased A-loop fluctuation and phosphorylation. KSR1/MEK1 complex has fewer interactions between KSR1 alpha G-helix and MEK1 A-loop, resulting in a more flexible A-loop.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Hansaim Lim, Fatma Cankara, Chung -Jung Tsai, Ozlem Keskin, Ruth Nussinov, Attila Gursoy
Summary: This review discusses recent advancements in computational methods for predicting microbial effects on human cells, with a focus on protein-protein interactions. Traditional methods, as well as more recent deep learning methods, are categorized and potential solutions to challenges in structure-based approaches are discussed. The review provides a brief guide to the current status and future directions in the field.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Chung -Jung Tsai, Hyunbum Jang
Summary: This article discusses the principles and applications of allosteric activating mutations and drugs, using examples from the Ras signaling network. Specifically, it focuses on Abl kinase mutations that shift the conformation towards an active state, leading to competition between high affinity ATP and drug binding. Recent pharmacological innovation includes allosteric inhibitors and allosteric heterobifunctional degraders that can destroy targets. The design of chemical linkers in bifunctional degraders allows precise coordination between the target protein and the E3 ubiquitin ligase, enabling innovative drug discovery.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Review
Multidisciplinary Sciences
Ruth Nussinov, Chung-Jung Tsai, Hyunbum Jang
Summary: Immunity plays a crucial role in both neurodevelopmental disorders and cancer, as the immune and nervous systems coevolve during embryonic development. Dysregulated signaling caused by germline or embryonic mutations can lead to changes in chromatin organization and gene accessibility, affecting the expression of essential genes in neurodevelopment. Similarly, dysregulated signaling resulting from somatic mutations contributes to cancer development. Both conditions involve small GTPases and their pathways, as well as dysregulation of TLRs, IL-1, GIT1, and FGFR signaling pathways. However, key differentiating factors are the timing and level of perturbation in specific cell types, indicating chromatin reorganization.
Article
Biochemistry & Molecular Biology
Patrick Grudzien, Hyunbum Jang, Nicholas Leschinsky, Ruth Nussinov, Vadim Gaponenko
Summary: This article summarizes the research findings on the exhaustion of CD8+ T cells in the tumor microenvironment induced by cholesterol, the reprogramming of tumor-associated macrophages and tumor progression driven by cholesterol efflux, and the inhibitory effects of statins on tumor growth.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yonglan Liu, Mingzhen Zhang, Hyunbum Jang, Ruth Nussinov
Summary: Bcr-Abl, a nonreceptor tyrosine kinase, plays a crucial role in leukemias, particularly chronic myeloid leukemia (CML). The fusion of Bcr and Abl leads to constitutive activation of Bcr-Abl. Oligomerization of Bcr-Abl is critical for its membrane clustering, MAPK signaling, and cell proliferation. Understanding the structural basis of Bcr-Abl oligomerization can guide the development of novel drugs targeting this process.
Letter
Oncology
Mingzhen Zhang, Ryan Maloney, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
CANCER COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Ruth Nussinov, Mingzhen Zhang, Yonglan Liu, Hyunbum Jang
Summary: Drug discovery is a highly challenging and significant interdisciplinary aim. The success of AlphaFold, an AI-powered technology, has raised hopes for drug discovery, but its limitations need to be considered. Improving AlphaFold's performance in active state models can enhance the success rate of rational drug design.
DRUG DISCOVERY TODAY
(2023)
Article
Chemistry, Physical
Mingzhen Zhang, Yonglan Liu, Hyunbum Jang, Ruth Nussinov
Summary: Kinase drug selectivity is a challenge in cancer research. Researchers propose a protocol to identify unique geometric features in the drug pocket that can distinguish one kinase from others. They analyze the structural principles of kinase drug selectivity using experimental structures and artificial intelligence. The results show that there are binary units in the kinome that can distinguish kinases from each other.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2023)
Review
Biophysics
Ruth Nussinov, Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Mingzhen Zhang, Yonglan Liu, Chung-Jung Tsai, Hyunbum Jang, Nurcan Tuncbag
Summary: Neurodevelopmental disorders (NDDs) and cancer have similarities in terms of proteins, pathways, and mutations, but have different clinical symptoms. However, individuals with NDDs have a higher likelihood of developing cancer later on. This review explores how shared features can result in different medical conditions and why having an NDD first can increase the chances of malignancy.
BIOPHYSICAL REVIEWS
(2023)
Article
Genetics & Heredity
Bengi Ruken Yavuz, M. Kaan Arici, Habibe Cansu Demirel, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov, Nurcan Tuncbag
Summary: Epidemiological studies show that individuals with neurodevelopmental disorders are more likely to develop certain types of cancer. While these disorders and cancer share proteins, pathways, and mutations, they differ in clinical outcomes. The key factor determining clinical outcome is signaling strength, with strong signaling promoting cell proliferation in cancer and moderate signaling affecting differentiation in neurodevelopmental disorders.
NPJ GENOMIC MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang
Summary: The propensities of protein conformations can predict cell function and suggest drug efficiency.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Ruth Nussinov, Yonglan Liu, Wengang Zhang, Hyunbum Jang
Summary: The sequence-structure-function paradigm in molecular biology has been updated to include the concept of conformational ensembles, recognizing that proteins are dynamic and constantly transitioning between different conformational states. The number and stability of these states are crucial for protein function. Understanding conformational propensities is essential for studying diverse systems and can provide insights into the dynamics of protein ensembles in cells.
RSC CHEMICAL BIOLOGY
(2023)
Article
Genetics & Heredity
Dana Mary Varghese, Ruth Nussinov, Shandar Ahmad
Summary: Moonlighting proteins are capable of performing multiple autonomous functions. In this study, human moonlighting DNA-binding proteins (mDBPs) were investigated and found to be distinguishable from other proteins with the same DNA-binding function. A machine learning model was developed to predict mDBPs from other DBPs with high accuracy.
NAR GENOMICS AND BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Yonglan Liu, Mingzhen Zhang, Chung-Jung Tsai, Hyunbum Jang, Ruth Nussinov
Summary: Researchers have used extensive molecular dynamics simulations to decipher the activation and autoinhibition mechanism of c-Abl. The myristoyl group serves as a switch for c-Abl inhibition/activation, and precise SH2/N-lobe interaction is required for full activation. Bcr-Abl allosteric drugs mimic the endogenous myristoyl-mediated autoinhibition state and alter the active-site conformation, affecting the action of ATP-competitive drugs.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Ankita Chadda, Alexander G. Kozlov, Binh Nguyen, Timothy M. Lohman, Eric A. Galburt
Summary: In this study, it was found that the DNA damage response in Mycobacterium tuberculosis differs from well-studied model bacteria. The DNA repair helicase UvrD1 in Mtb is activated through a redox-dependent process and is closely associated with the homo-dimeric Ku protein. Additionally, Ku protein is shown to stimulate the helicase activity of UvrD1.
JOURNAL OF MOLECULAR BIOLOGY
(2024)
