Article
Clinical Neurology
Angel Edo, Laura Calvo-Barreiro, Herena Eixarch, Assumpcio Bosch, Miguel Chillon, Carmen Espejo
Summary: This study developed a gene therapy strategy to block the interaction between interleukin 21 and its receptor in a murine model of experimental autoimmune encephalomyelitis. The results showed different clinical effects depending on the timing of treatment, highlighting the pleiotropicity of this cytokine in different stages of the disease.
Article
Immunology
Mengxiao Luo, Biao Zhou, Eswar R. Reddem, Bingjie Tang, Bohao Chen, Runhong Zhou, Hang Liu, Lihong Liu, Phinikoula S. Katsamba, Ka-Kit Au, Hiu-On Man, Kelvin Kai-Wang To, Kwok-Yung Yuen, Lawrence Shapiro, Shangyu Dang, David D. Ho, Zhiwei Chen
Summary: In this study, the diversity, potency, breadth, and structural insights of bNAbs derived from memory B cells of BNT162b2-vaccinated individuals after Omicron BA.1 breakthrough infection were determined. The infection activated diverse memory B cell clonotypes that generated potent class I/II and III bNAbs with new epitopes mapped to the receptor-binding domain (RBD). While the top eight bNAbs neutralized wildtype and BA.1 effectively, they displayed different IgH/IgL sequences and neutralization profiles against other variants of concern (VOCs). Two class III NAbs, P2D9 and P3E6, showed comparable potency against BA.4/BA.5, but structural analysis revealed distinct modes of action. P3E6 neutralized all tested variants through a unique bivalent interaction with two RBDs. These findings provide new insights into the hybrid immunity generated by BNT162b2-induced diverse memory B cells in response to Omicron breakthrough infection.
EMERGING MICROBES & INFECTIONS
(2023)
Article
Biochemistry & Molecular Biology
Caleb R. Glassman, Yamuna Kalyani Mathiharan, Kevin M. Jude, Leon Su, Ouliana Panova, Patrick J. Lupardus, Jamie B. Spangler, Lauren K. Ely, Christoph Thomas, Georgios Skiniotis, K. Christopher Garcia
Summary: The structural mechanism of receptor sharing used by IL-12 family cytokines can be utilized to tune the cytokine axis for therapeutics, as demonstrated by the design of IL-12 partial agonists that elicited anti-tumor immunity in vivo.
Review
Immunology
Charles D. Murin, Pavlo Gilchuk, James E. Crowe, Andrew B. Ward
Summary: This review describes how structural biology has revealed the molecular basis of broad ebolavirus neutralization, and discusses the history of monoclonal antibody therapeutics for ebolaviruses, as well as key structural studies that have advanced our understanding of ebolavirus glycoprotein structures and antibody-mediated neutralization.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Arnaud Goepfert, Carmen Barske, Sylvie Lehmann, Emmanuelle Wirth, Joschka Willemsen, Johann E. Gudjonsson, Nicole L. Ward, Mrinal K. Sarkar, Rene Hemmig, Frank Kolbinger, Jean-Michel Rondeau
Summary: Through crystallography, biophysics, and mutational studies, this research demonstrates that IL-17A, IL-17F, and IL-17A/F induce IL-17RA dimerization, leading to the formation of a 2:2:2 hexameric signaling assembly. The formation of the IL-17 signalosome potentiates IL-17-induced IL-36 gamma and CXCL1 mRNA expression in human keratinocytes compared to a dimerization-defective IL-17RA variant.
Article
Immunology
Holly Bachus, Erin McLaughlin, Crystal Lewis, Amber M. Papillion, Etty N. Benveniste, Dave Durell Hill, Alexander F. Rosenberg, Andre Ballesteros-Tato, Beatriz Leon
Summary: Defective IL-6 signaling is linked to Th2 bias and elevated IgE levels. The study reveals that IL-6 signaling in allergen-specific T cells is necessary to prevent Th2 cell differentiation, IgE response, and allergic inflammation. IL-6 inhibits IL-2 signaling through upregulation of SOCS3, thus preventing Th2 priming.
CELLULAR & MOLECULAR IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Jianjie Zhou, Yu Xiao, Yifei Ren, Jiwan Ge, Xinquan Wang
Summary: The TIR domains in the IL-1R family play a crucial role in signal transmission, and the structurally variant regions and key residues in the helices greatly impact the signaling process.
Article
Biochemistry & Molecular Biology
Stefan Rose-John
Summary: IL-6 is a cytokine involved in immunity, neural cell maintenance, and metabolism. It is synthesized by various cells and its levels are elevated during infection and inflammation. IL-6 binds to a receptor complex and can also act on cells without the IL-6 receptor through trans-signaling.
Article
Multidisciplinary Sciences
Chang Liu, Wei Shi, Scott T. Becker, David G. Schatz, Bin Liu, Yang Yang
Summary: This study highlights the crucial role of ExoN in the coronavirus life cycle, its recognition and excision of nucleotide analog inhibitors, and provides insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. The cryo-electron microscopy structures reveal the molecular determinants of ExoN substrate specificity, offering guidance for the rational design of improved anticoronavirus therapies.
Article
Immunology
Shannon M. Kahan, Rakesh K. Bakshi, Jennifer T. Ingram, R. Curtis Hendrickson, Elliot J. Lefkowitz, David K. Crossman, Laurie E. Harrington, Casey T. Weaver, Allan J. Zajac
Summary: The ability to produce IL-2 identifies constituents of the expanded CD8 T cell effector pool with stem-like features, which exhibit superior protective powers. The production of IL-2 by cells attenuates the ability to receive IL-2 signals, limiting terminal effector formation and conferring superior protection. Non-producing effector cells, on the other hand, gain effector traits at the expense of memory formation. Despite distinct properties during the effector phase, IL-2-producing and non-producing CD8 T cells converge transcriptionally as memory matures, forming populations with equal recall abilities.
SCIENCE IMMUNOLOGY
(2022)
Article
Immunology
Bao Zhao, Weipeng Gong, Anjun Ma, Jianwen Chen, Maria Velegraki, Hong Dong, Zihao Liu, Lingling Wang, Tamio Okimoto, Devin M. Jones, Yu L. Lei, Meixiao Long, Kenneth J. Oestreich, Qin Ma, Gang Xin, David P. Carbone, Kai He, Zihai Li, Haitao Wen
Summary: The study suggests that SUSD2 acts as a negative regulator of CD8(+) T cells in the tumor microenvironment by interfering with the IL-2 receptor alpha and suppressing the binding of IL-2 to the receptor. Dysfunctional CD8(+) T cells, which fail to produce effective antitumor molecules, contribute to immunosuppression in tumors. The researchers found that altering SUSD2 expression enhances the production of antitumor molecules in CD8(+) T cells, leading to reduced tumor growth in mouse models, indicating the potential of SUSD2 as a target for cancer immunotherapy.
Article
Immunology
Maolin Ma, Qipeng Sun, Xiujie Li, Gengguo Deng, Yannan Zhang, Zhe Yang, Fei Han, Zhengyu Huang, Youqiang Fang, Tao Liao, Qiquan Sun
Summary: This study investigated the effect of IL-6/IL-6R signaling blockade on acute antibody-mediated rejection (AAMR) and found that the blockade significantly reduced graft injury and improved survival. Mechanistic research showed that the blockade decreased B cell numbers, inhibited antibody production and complement activation, and reduced inflammatory cell infiltration in allografts.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Plant Sciences
Young Yun Jung, Jae-Young Um, Omaima Nasif, Sulaiman Ali Alharbi, Gautam Sethi, Kwang Seok Ahn
Summary: Leelamine (LEE) inhibits STAT3 phosphorylation and up-stream signaling molecules, leading to cell cycle arrest and enhanced apoptosis in multiple myeloma cells. When used in combination with bortezomib, it synergistically enhances apoptotic actions against MM cells.
Article
Multidisciplinary Sciences
Reza Alimohammadi, Ghanbar Mahmoodi Chalbatani, Masoumeh Alimohammadi, Haniyeh Ghaffari-Nazari, Arezou Rahimi, Esmail Mortaz, Nariman Mossafa, Louis Boon, Seyed Amir Jalali
Summary: This study demonstrated that the combination therapy of FOLFOX, CD47, and PD-L1 blocking antibodies effectively increased survival and reduced tumor size in a CT-26 mouse tumor model. The triple combining regimen also resulted in a decrease in Treg and MDSC, as well as an increase in CD8+ INF-gamma+ lymphocytes and M1/M2 macrophage ratio in the tumor microenvironment. The findings suggest that this combination therapy has the potential to be translated into clinical practice.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Jason A. Hackney, Haridha Shivram, Jason Vander Heiden, Chris Overall, Luz Orozco, Xia Gao, Eugene Kim, Nathan West, Aditi Qamra, Diana Chang, Arindam Chakrabarti, David F. Choy, Alexis J. Combes, Tristan Courau, Gabriela K. Fragiadakis, Arjun Arkal Rao, Arja Ray, Jessica Tsui, Kenneth Hu, Nicholas F. Kuhn, Matthew F. Krummel, David J. Erle, Kirsten Kangelaris, Aartik Sarma, Zoe Lyon, Carolyn S. Calfee, Prescott G. Woodruff, Rajani Ghale, Eran Mick, Ashley Byrne, Beth Shoshana Zha, Charles Langelier, Carolyn M. Hendrickson, Monique G. P. van der Wijst, George C. Hartoularos, Tianna Grant, Raymund Bueno, David S. Lee, John R. Greenland, Yang Sun, Richard Perez, Anton Ogorodnikov, Alyssa Ward, Chun Jimmie Ye, Ucsf comet Consortium, Thiru Ramalingam, Jacqueline M. Mcbride, Fang Cai, Anastasia Teterina, Min Bao, Larry Tsai, Ivan O. Rosas, Aviv Regev, Sharookh B. Kapadia, Rebecca N. Bauer, Carrie M. Rosenberger
Summary: Altered myeloid inflammation and lymphopenia are characteristic features of severe infections. This study identified an upregulated EN-RAGE gene program in airway and blood myeloid cells from patients with acute lung injury, including those with SARS-CoV-2 infection. The expression of this program was associated with clinical severity, mechanical ventilation, and death. IL-6 was identified as a key driver of myeloid dysregulation, and blockade of IL-6 signaling normalized the expression of EN-RAGE and T cell genes.
Article
Biochemistry & Molecular Biology
Xiaolin Zeng, Xinchen Lv, Rui Liu, Hang He, Shiqi Liang, Lixian Chen, Fan Zhang, Liu Chen, Yuehui He, Jiamu Du
Summary: The transcription factor CONSTANS (CO) forms a head-to-tail oligomeric configuration via its B-boxes to mediate the activation of florigen FLOWERING LOCUS T (FT) in long days. The multimerization of CO is crucial for its functionality.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Yifan Zhang, Ziyue Chen, Fang Wang, Honghua Sun, Xueliang Zhu, Jianping Ding, Tianlong Zhang
Summary: This study demonstrates that Rab9 utilizes Nde1 as an effector to interact with the dynein motor complex, thereby tethering the late endosomes to the dynein motor for their retrograde transport to the TGN.
Review
Plant Sciences
Hongmiao Hu, Jiamu Du
Summary: This review focuses on the central role of histone methylation in regulating chromatin state and gene expression in Arabidopsis. It summarizes the current understanding of the dynamic regulation of histone methylation, with a particular emphasis on the histone methyltransferases and demethylases involved.
CURRENT OPINION IN PLANT BIOLOGY
(2022)
News Item
Biochemistry & Molecular Biology
Sisi Li, Jiamu Du
Summary: A fungal TET dioxygenase homolog, CcTet, was found to have demethylase activity for both 5-methylcytosine (5mC) and N-6-methyladenine (6mA). Structure-based engineering of CcTet resulted in a 6mA-specific demethylase, which provides a useful tool for manipulating and studying 6mA.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Xuan Du, Zhenlin Yang, Alfredo Jose Florez Ariza, Qian Wang, Guohui Xie, Sisi Li, Jiamu Du
Summary: This study determined the structure of maize RNA-DEPENDENT RNA POLYMERASE 2 (ZmRDR2) and found both active and inactive conformations, providing insights into the molecular mechanism of dsRNA synthesis during plant siRNA production.
Article
Ecology
Suhui Lv, Yu Yang, Gang Yu, Li Peng, Shuai Zheng, Sunil Kumar Singh, Juan Ignacio Vilchez, Richa Kaushal, Hailing Zi, Dian Yi, Yuhua Wang, Shaofan Luo, Xiaoxuan Wu, Ziwei Zuo, Weichang Huang, Renyi Liu, Jiamu Du, Alberto P. Macho, Kai Tang, Huiming Zhang
Summary: Root microbiota is crucial for plant growth and fitness, and the assembly of root microbiota may be controlled by epigenetic regulation. In Arabidopsis thaliana, dysfunction of the histone demethylase IBM1 significantly reshaped the root microbiota. Epigenetic modifications imposed by IBM1-dependent regulation affect plant growth, immunity, and interactions with beneficial and pathogenic bacteria.
Correction
Biochemistry & Molecular Biology
Sisi Li, Jiamu Du
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Xin Tang, Yifan Zhang, Guanchao Wang, Chunxiao Zhang, Fang Wang, Jiawen Shi, Tianlong Zhang, Jianping Ding
Summary: The mTORC1 complex is a central regulator of cell growth and metabolism, and SAMTOR functions as a sensor for S-adenosylmethionine (SAM) to regulate mTORC1 activity. In this study, the crystal structures of SAMTOR in its apo form and bound to SAM were determined, revealing the mechanism of SAM sensing and its functional role in mTORC1 signaling.
Article
Multidisciplinary Sciences
Guohui Xie, Xuan Du, Hongmiao Hu, Sisi Li, Xiaofeng Cao, Steven E. Jacobsen, Jiamu Du
Summary: In this study, the structures of plant-specific polymerases Pols IV and V, which produce noncoding RNA in the RNA-directed DNA methylation pathway, were reported. The interaction between a conserved tyrosine residue of NRPE2 and double-stranded DNA branch in the transcription bubble suggests potential transcription stalling and attenuation of elongation. NRPE2 captures the nontemplate DNA strand to enhance backtracking and 3'-5' cleavage, allowing Pol V to maintain high fidelity. Furthermore, the structures provide insights into the mechanism of transcription stalling and enhanced backtracking by Pol V, supporting its function in tethering downstream factors for RNA-directed DNA methylation on chromatin.
Article
Biochemistry & Molecular Biology
Guanchao Wang, Xueqian Feng, Jianping Ding
Summary: In this study, the T95R mutation in the IRF4 gene was found to enhance the binding affinity and specificity of the IRF4 protein to DNA, with the highest preference for the noncanonical DNA sequence GATA.
Letter
Cell Biology
Yu Shi, Hui Yang, Jianping Ding
JOURNAL OF MOLECULAR CELL BIOLOGY
(2023)
Article
Plant Sciences
Xuan Du, Zhenlin Yang, Guohui Xie, Changshi Wang, Laixing Zhang, Kaige Yan, Maojun Yang, Sisi Li, Jian-Kang Zhu, Jiamu Du
Summary: The plant-specific ROS1/DME enzyme family can directly remove 5-methyl-cytosine, resulting in efficient DNA demethylation. The cryo-electron microscopy structures of the Arabidopsis ROS1 catalytic fragment in complex with substrate DNA, mismatch DNA, and reaction intermediate were determined. The substrate 5-methyl-cytosine is flipped-out from the DNA duplex and recognized by the ROS1 base-binding pocket through hydrophobic and hydrogen-bonding interactions. The protonation states of the bases determine the substrate preference for 5-methyl-cytosine over T:G mismatch. The study provides insights into the substrate specificity and reaction mechanism of the ROS1/DME family of plant-specific DNA demethylases.
Article
Biochemistry & Molecular Biology
Deyue Yang, Fengli Zhao, Danling Zhu, Xi Chen, Xiangxiong Kong, Yufeng Wu, Min Chen, Jiamu Du, Li-Jia Qu, Zhe Wu
Summary: The RNA-binding protein RZ-1 and the polycomb complex 2 (PRC2) work together to silence ABA biosynthesis genes and ensure seed germination.
Article
Biology
Qian Wang, Yan Xue, Laixing Zhang, Zhenhui Zhong, Suhua Feng, Changshi Wang, Lifan Xiao, Zhenlin Yang, C. Jake Harris, Zhe Wu, Jixian Zhai, Maojun Yang, Sisi Li, Steven E. Jacobsen, Jiamu Du
Summary: A protocol was developed to evaluate the in vitro dicing activity of DCL3 in Arabidopsis, involving cutting pre-siRNA into a siRNA duplex which can be visualized and quantified using label-free fluorescence SYBR Gold on urea PAGE. This cost-effective and hazard-free method has the potential to be adapted for other Dicers and small RNAs.
Correction
Biochemistry & Molecular Biology
Daoheng Hu, Yiming Yu, Chun Wang, Yanping Long, Yue Liu, Li Feng, Dongdong Lu, Bo Liu, Jinbu Jia, Rui Xia, Jiamu Du, Xuehua Zhong, Lei Gong, Kejian Wang, Jixian Zhai