Article
Oncology
Sundaramoorthy Revathidevi, Avaniyapuram Kannan Murugan, Hirofumi Nakaoka, Ituro Inoue, Arasambattu Kannan Munirajan
Summary: Cervical cancer, a common cancer in women, is primarily caused by HPV infection. Apart from genetic and epigenetic factors, the APOBEC3 family plays a crucial role in the molecular pathogenesis of cancer, including inducing tumor mutations through DNA editing mechanisms.
Review
Virology
Ananda Ayyappan Jaguva Vasudevan, Daniel Becker, Tom Luedde, Holger Gohlke, Carsten Munk
Summary: Non-human primates are a significant source of viruses that can be transmitted to humans, including a unique class of retroviruses called foamy viruses. These viruses are common in various mammalian natural hosts but not in humans, and their viral life cycle differs significantly from other retroviruses. Foamy viruses can replicate in the presence of many well-defined retroviral restriction factors, presenting unique challenges for understanding their interaction with host cells.
Article
Multidisciplinary Sciences
Fumiaki Ito, Ana L. Alvarez-Cabrera, Kyumin Kim, Z. Hong Zhou, Xiaojiang S. Chen
Summary: The study reveals the mechanism by which HIV-1 virus evades the antiviral response of human APOBEC3 (A3) cytidine deaminases. The cryo-EM structures of the viral infectivity factor (Vif) in complex with A3H, CBF-ss, and components of CUL5 ubiquitin ligase shed light on the interplay between HIV and humans.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Takuya Tada, Thomas D. Norton, Rebecca Leibowitz, Nathaniel R. Landau
Summary: This study demonstrated that direct injection of antigen-expressing lentiviral vectors could induce protective T cell responses against viral infection and cancer in animal models, showing potential for both preventative and therapeutic vaccination strategies.
Article
Biochemistry & Molecular Biology
Kyumin Kim, Alan B. Shi, Kori Kelley, Xiaojiang S. Chen
Summary: The APOBEC3 family of human cytidine deaminases, including APOBEC3A (A3A) and an APOBEC3B (A3B) chimera, are involved in cellular RNA editing. A3A has a preference for specific RNA substrates that are not efficiently deaminated by other APOBEC members. The efficiency of A3A's editing is influenced by RNA sequence contexts and stem-loop secondary structures. These findings provide insights into the intracellular RNA editing properties of A3A and the potential impact of A3A-mediated RNA editing.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Hanjing Yang, Kyumin Kim, Shuxing Li, Josue Pacheco, Xiaojiang S. Chen
Summary: Research has found that APOBEC3G restricts HIV infectivity through its binding to HIV RNA, and the mechanism of APOBEC3G capturing viral RNA is via specific recognition of unpaired dinucleotides. This RNA recognition is critical for APOBEC3G's antiviral function.
NATURE COMMUNICATIONS
(2022)
Article
Virology
Shota Tsukimoto, Yoshiyuki Hakata, Sachiyo Tsuji-Kawahara, Takuji Enya, Tetsuo Tsukamoto, Seiya Mizuno, Satoru Takahashi, Shinichi Nakao, Masaaki Miyazawa
Summary: APOBEC3 protein is expressed at distinctively high levels in germinal center B cells of mice, and antigenic stimulation does not affect the expression levels of APOBEC3 protein.
Article
Multidisciplinary Sciences
Sunwoo Oh, Elodie Bournique, Danae Bowen, Pegah Jalili, Ambrocio Sanchez, Ian Ward, Alexandra Dananberg, Lavanya Manjunath, Genevieve P. Tran, Bert L. Semler, John Maciejowski, Marcus Seldin, Remi Buisson
Summary: This study uncovers the mechanisms by which viral infection and genotoxic stress transiently up-regulate APOBEC3A and other pro-inflammatory genes through multiple pathways.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Wenzhi Song, Olivia Q. Antao, Emily Condiff, Gina M. Sanchez, Irene Chernova, Krzysztof Zembrzuski, Holly Steach, Kira Rubtsova, Davide Angeletti, Alexander Lemenze, Brian J. Laidlaw, Joe Craft, Jason S. Weinstein
Summary: Tbet(+)CD11c(+) B cells are a specific subset of B cells that arise during immune challenges, aging, and autoimmune processes. T follicular helper (Tfh) cells were found to drive the generation of Tbet(+)CD11c(+) B cells, which develop prior to germinal center formation and have distinct phenotypic and transcriptional profiles from germinal center B cells. Fate tracking revealed that the development of most Tbet(+)CD11c(+) B cells is independent of germinal center entry and cell-intrinsic Bcl6 expression. These cells form a competitive memory subset in the marginal zone and contribute to efficient antibody production and secondary germinal center seeding upon rechallenge.
Article
Multidisciplinary Sciences
Hai-Jian Huang, Yi-Yuan Li, Zhuang-Xin Ye, Li-Li Li, Qing-Ling Hu, Yu-Juan He, Yu-Hua Qi, Yan Zhang, Ting Li, Gang Lu, Qian-Zhuo Mao, Ji-Chong Zhuo, Jia-Bao Lu, Zhong-Tian Xu, Zong-Tao Sun, Fei Yan, Jian-Ping Chen, Chuan-Xi Zhang, Jun-Min Li
Summary: Non-retroviral endogenous viral elements (nrEVEs) are widely dispersed in eukaryotic genomes, with their functions largely unknown. In this study, researchers discovered that a ToEVE in planthoppers has been domesticated and plays essential roles in their development and reproduction. Analysis of arthropod genomes suggests that nrEVEs may contribute to the functional diversity of arthropod genes.
NATURE COMMUNICATIONS
(2023)
Article
Virology
Shana M. Owens, Darby G. Oldenburg, Douglas W. White, J. Craig Forrest
Summary: Gammaherpesviruses establish lifelong chronic infections in immune cells, and gene products like M2 play a critical role in promoting viral reactivation and dissemination within the host. This study demonstrates that M2 function is specific to B cells, particularly AID-expressing cells, and is essential for GHV pathogenesis in murine models. The use of a viral genetic system allowed for the identification of cell-type-specific requirements for M2 and highlighted the importance of viral latency genes in host colonization.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Francesc Catala-Moll, Anna G. Ferrete-Bonastre, Tianlu Li, Dieter Weichenhan, Pavlo Lutsik, Laura Ciudad, Angel F. Alvarez-Prado, Javier Rodriguez-Ubreva, Christian Klemann, Carsten Speckmann, Amaya Vilas-Zornoza, Hassan Abolhassani, Monica Martinez-Gallo, Romina Dieli-Crimi, Jacques G. Riviere, Andrea Martin-Nalda, Roger Colobran, Pere Soler-Palacin, Sven Kracker, Lennart Hammarstrom, Felipe Prosper, Anne Durandy, Bodo Grimbacher, Christoph Plass, Esteban Ballestar
Summary: The study investigated the role of AID in active DNA demethylation in germinal center B cells, finding that AID is not directly involved in it and the DNA methylation alterations in HIGM2 B cells are mainly caused by premature B-cell receptor overstimulation. These results support the crucial role of AID in B cell central tolerance.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Virology
Janina Deutschmann, Thomas Gramberg
Summary: SAMHD1 is a crucial enzyme in cells that plays a role in balancing dNTP concentrations, promoting DNA damage repair, and suppressing immune responses, while also acting as a major restriction factor against various viruses. Some viruses are efficiently restricted by SAMHD1, but others have developed evasion mechanisms to counteract its antiviral activity.
Review
Chemistry, Medicinal
Qiqi Bao, Jinming Zhou
Summary: The host restriction factor APOBEC3G (A3G) restricts Vif-deficient HIV-1 replication by causing mutations during viral DNA synthesis. HIV-1 expresses Vif protein to counteract A3G by degrading it. The self-association of Vif with A3G proteins, chaperones, and factors of the ubiquitination machinery is a potential target for novel anti-HIV drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Amanda E. Ward, Daria Sokovikova, Melvin Neal Waxham, Frederick A. Heberle, Ilya Levental, Kandice R. Levental, Volker Kiessling, Judith M. White, Lukas K. Tamm
Summary: Serinc5 is a host restriction factor that inhibits the infection of budding HIV particles, but its mechanism is not fully understood. It has been found that Serinc5 can alter the conformation and clustering of the HIV fusion protein Env. By measuring pseudoviral membrane thickness and order, it was found that Serinc5 increases membrane heterogeneity and promotes the formation of ordered phase in the viral membrane. The presence of phosphatidylethanolamine (PE) can rescue HIV pseudovirus fusion from Serinc5 restriction, accompanied by decreased membrane heterogeneity and order.
ACS INFECTIOUS DISEASES
(2023)
Article
Biochemistry & Molecular Biology
Blake T. Riley, Stephanie A. Wankowicz, Saulo H. P. de Oliveira, Gydo C. P. van Zundert, Daniel W. Hogan, James S. Fraser, Daniel A. Keedy, Henry van den Bedem
Summary: The new qFit 3 software automates the analysis of dynamic protein structure data by generating a multi-conformer model, providing important insights for biological research. The software has been improved to run efficiently on small servers, desktops, or laptops. qFit 3 is open-source and available at the specified URL.
Review
Virology
Amit Gaba, Ben Flath, Linda Chelico
Summary: The transmission of viruses from animal hosts to humans has led to the emergence of various diseases. Host restriction factors usually block these cross-species transmissions, but viral antagonist proteins can evolve to suppress restriction factors in new hosts, enabling cross-species transmission. An example of this is the APOBEC3-Vif interface and its impact on HIV in humans.
Article
Immunology
Aizhang Xu, Scot C. Leary, Md Fahmid Islam, Zhaojia Wu, Kalpana Kalyanasundaram Bhanumathy, Anjuman Ara, Rajni Chibbar, Andrew Fleywald, Khawaja Ashfaque Ahmed, Jim Xiang
Summary: This study reveals that the weak strength of IL-7-activated mTORC1-S6K signaling controls T cell memory through the activation of transcriptional and metabolic pathways, greatly impacting vaccine development.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Vijay Jayaraman, D. John Lee, Nadav Elad, Shay Vimer, Michal Sharon, James S. Fraser, Dan S. Tawfik
Summary: This study discovered a 1.6 megadalton multi-enzyme complex made up of glutamate synthase and glutamate dehydrogenase, which have opposite functions, in Bacillus subtilis. The complex inhibits the activity of glutamate dehydrogenase and is essential for cell growth under fluctuating glutamate concentrations.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Kaitlyn Tsai, Vanja Stojkovic, D. John Lee, Iris D. Young, Teresa Szal, Dorota Klepacki, Nora Vazquez-Laslop, Alexander S. Mankin, James S. Fraser, Danica Galonic Fujimori
Summary: Linezolid and radezolid are oxazolidinone antibiotics that inhibit bacterial ribosome translation by binding to the peptidyl transferase center in a context-specific manner, leading to stalling when alanine occupies the penultimate position in the nascent chain.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Cody Krivacic, Kale Kundert, Xingjie Pan, Roland A. Pache, Lin Liu, Shane O. Conchuir, Jeliazko R. Jeliazkov, Jeffrey J. Gray, Michael C. Thompson, James S. Fraser, Tanja Kortemme
Summary: The article introduces two computational methods (FKIC and LHKIC) capable of generating and predicting new local protein geometries. These methods were used to create a design protocol (PIP) to position functionally important side chains in proteins, resulting in the engineering of new protein functions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Stephanie A. Wankowicz, Saulo H. de Oliveira, Daniel W. Hogan, Henry van den Bedem, James S. Fraser
Summary: This study measured conformational heterogeneity in a large number of crystallographic datasets and found that binding site residues become more rigid upon ligand binding, while distant residues become more flexible, especially in non-solvent-exposed regions. Additionally, protein flexibility was observed to increase as the number of hydrogen bonds decreases and relative hydrophobicity increases.
Editorial Material
Immunology
Yuqing Feng, Alberto Martin
Summary: This article highlights a gene repair mechanism that allows B cells to carry out mutagenic DNA repair, which is essential for antibody maturation and has implications in cancer pathogenesis.
TRENDS IN IMMUNOLOGY
(2022)
Editorial Material
Biotechnology & Applied Microbiology
Jennifer M. Michaud, Ali Madani, James S. Fraser
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Manfred S. Weiss, Jan Wollenhaupt, Galen J. Correy, James S. Fraser, Andreas Heine, Gerhard Klebe, Tobias Krojer, Marjolein Thunnissen, Nicholas M. Pearce
Summary: Jaskolski et al. analyzed diffraction data sets from fragment-screening group depositions and claimed that these data are problematic. However, we demonstrate that none of the criticisms persist if the data are treated properly.
Article
Virology
Fareeda M. Barzak, Timothy M. Ryan, Nazanin Mohammadzadeh, Stefan Harjes, Maksim Kvach, Harikrishnan M. Kurup, Kurt L. Krause, Linda Chelico, Vyacheslav V. Filichev, Elena Harjes, Geoffrey B. Jameson
Summary: This study investigates the solution-state structures of full-length APOBEC3G with and without ssDNA using small-angle X-ray scattering (SAXS). The results reveal the formation of a complex between full-length APOBEC3G and ssDNA, explaining the disappearance of dimers and the dominance of monomeric protein species when ssDNA is added.
Article
Multidisciplinary Sciences
Filip Yabukarski, Tzanko Doukov, Margaux M. Pinney, Justin T. Biel, James S. Fraser, Daniel Herschlag
Summary: Decades of structure-function studies have provided extensive understanding of enzymes, but traditional structural models can only capture snapshots of conformational ensembles. By studying ketosteroid isomerase, researchers demonstrate the importance of conformational ensembles in understanding enzyme function. Ensemble-function analyses reveal the effects of changing conformation probabilities and reactivity on enzyme function, which is crucial for advancing our knowledge of enzymes and developing new ones.
Article
Biochemical Research Methods
David C. Wych, Phillip C. Aoto, Lily Vu, Alexander M. Wolff, David L. Mobley, James S. Fraser, Susan S. Taylor, Michael E. Wall
Summary: This article investigates the use of molecular-dynamics (MD) simulations to improve macromolecular crystallography (MX) studies. By combining MD simulations with conventional modeling and refinement tools, the authors were able to improve the interpretation of ambiguous density in protein crystals, leading to more accurate protein models and mechanistic insights into enzyme interactions.
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2023)
Article
Virology
Maria Yousefi, Arun Kumar Annan Sudarsan, Amit Gaba, Linda Chelico
Summary: APOBEC3 enzymes can restrict HIV-1 replication, with APOBEC3F being able to hetero-oligomerize with APOBEC3H haplotype I, increasing resistance to Vif and enhancing HIV-1 restriction.
Article
Multidisciplinary Sciences
Do-Hyun Kim, Yilin Wang, Haerin Jung, Rachael L. Field, Xinya Zhang, Ta-Chiang Liu, Changqing Ma, James S. Fraser, Jonathan R. Brestoff, Steven J. Van Dyken
Summary: This study describes a mammalian adaptation to dietary chitin through gastric immune activation and acidic mammalian chitinase, which facilitates chitin digestion. This adaptation is preserved in germ-free mice and leads to enhanced metabolic health and resistance to obesity.