Review
Biochemistry & Molecular Biology
Anna G. Mankovich, Brian C. Freeman
Summary: Heat shock protein 90 (Hsp90), a highly conserved molecular chaperone, not only maintains the stability of metastable proteins, but also plays a crucial role in protein transport. The specific contributions of Hsp90 to protein transport are still not well defined, despite numerous connections with factors involved in this process.
Review
Biochemistry & Molecular Biology
Abhinav Joshi, Takeshi Ito, Didier Picard, Len Neckers
Summary: TRAP1 is an important mitochondrial molecular chaperone that regulates mitochondrial respiration and homeostasis, while also displaying cytoprotective activity. It is involved in neurodegenerative diseases and multiple cancers.
Review
Chemistry, Medicinal
Lei Wang, Qiuyue Zhang, Qidong You
Summary: Heat shock protein 90 (HSP90) is crucial in cancer cells, but its inhibitors have limited efficacy and side effects. Researchers are investigating the disruption of the HSP90-CDC37-kinase complex as an alternative solution to avoid limitations.
MEDICINAL RESEARCH REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Changhoon Lee, Ho Jin Youn, Sang-Hoon Lee, Jinwoo Kim, Daeyoung Son, Joon-Yung Cha
Summary: This study investigated the positive role of plant Aha in heat stress tolerance through chaperone properties and/or activation of Hsp90 to protect substrate proteins from thermal injury.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Samarpan Maiti, Didier Picard
Summary: The heat shock protein 90 (Hsp90) is a crucial molecular chaperone and regulator of protein stability in both normal and stressful conditions. In mammals, there are two cytosolic isoforms of Hsp90, Hsp90 alpha and Hsp90 beta, which have overlapping functions and interact with a majority of the proteome. Recent studies suggest that there may be differences in the specific functions of these isoforms, particularly in relation to certain tissues or cell types. Understanding the isoform-specific functions is important for designing therapeutic strategies.
Article
Biochemistry & Molecular Biology
Laura Perna, Matteo Castelli, Elena Frasnetti, Lisa E. L. Romano, Giorgio Colombo, Chrisostomos Prodromou, J. Paul Chapple
Summary: In this study, an AlphaFold structure of sacsin was compared with yeast Hsp90, revealing novel insights into the structure of sacsin. Residues within sacsin's Hsp90-like domains required for ATP binding and hydrolysis were identified, including catalytic arginine residues equivalent to Hsp90's middle domain. This study supports the hypothesis that sacsin functions as an ATP-driven super molecular chaperone.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Maximilian M. Biebl, Abraham Lopez, Alexandra Rehn, Lee Freiburger, Jannis Lawatscheck, Birgit Blank, Michael Sattler, Johannes Buchner
Summary: The study shows that a tryptophan residue in the proximal region of the p23 tail decelerates the ATPase of Hsp90 by altering the conformation of the catalytic loop, while a conserved helical motif in the p23 tail interacts with the client protein binding site of Hsp90 and is involved in the activation of the client protein in the cellular context.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Sara Garcia-Alonso, Pablo Mesa, Laura de la Puente Ovejero, Gonzalo Aizpurua, Carmen G. Lechuga, Eduardo Zarzuela, Clara M. Santiveri, Manuel Sanclemente, Javier Munoz, Monica Musteanu, Ramon Campos-Olivas, Jorge Martinez-Torrecuadrada, Mariano Barbacid, Guillermo Montoya
Summary: This study describes the structure of the RAF1 protein in complex with HSP90 and CDC37. The research reveals that CDC37 can differentiate between different members of the RAF family. Additionally, the study shows that folded RAF1 assembles with 14-3-3 dimers, and disrupting the interaction between CDC37 and RAF1 may have potential therapeutic implications.
Article
Chemistry, Analytical
Helisa H. Wippel, Juan D. Chavez, Andrew D. Keller, James E. Bruce
Summary: The XL-MS technique provides insight into protein conformations and interactions within their cellular environment, while the iqPIR strategy allows for comparative interactome studies using isotope encoded chemical cross-linkers. Multiplexed iqPIR enables quantitative interactome analysis of up to six biological samples in a single LC-MS acquisition, revealing specific protein conformational and interaction changes in response to different inhibitors.
ANALYTICAL CHEMISTRY
(2022)
Review
Cell Biology
Melissa Louise Stofberg, Celine Caillet, Marianne de Villiers, Tawanda Zininga
Summary: Malaria remains a major killer parasitic disease in tropical settings, with the development of antimalarial drug resistance posing a significant challenge in disease control. Therefore, there is a need to explore new strategies and treatment options to reverse the development of antimalarial drug resistance.
Article
Chemistry, Multidisciplinary
Chuan-jing Cheng, Kai-xin Liu, Man Zhang, Fu-kui Shen, Li-li Ye, Wen-bo Wu, Xiao-tao Hou, Er-wei Hao, Yuan-yuan Hou, Gang Bai
Summary: This study identified a novel natural inhibitor of HSP90, okicamelliaside (OCS), which selectively inhibits the formation of the HSP90-CDC37 protein complex and disrupts protein-protein interactions of HSP90-CDC37 to exert anti-tumor effects.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Engineering, Environmental
Yuqing Tang, Dongju Zhao, Fan Yang, Gaoju Pang, Zuhao Sun, Jin Chang, Yan Dou
Summary: This study constructs HMPB-AAG nanoagents, which achieve a combinational therapeutic effect on tau-related pathology by reducing p-tau levels, alleviating oxidative stress and neuroinflammation, and inhibiting neuronal apoptosis and synaptic damage.
CHEMICAL ENGINEERING JOURNAL
(2022)
Article
Chemistry, Medicinal
Oi Wei Mak, Nabangshu Sharma, Johannes Reynisson, Ivanhoe K. H. Leung
Summary: Heat shock protein 90 (Hsp90) is a crucial molecular chaperone in cells, serving important functions in stress response and maintenance, and is currently targeted for cancer treatment. Two novel drug-like Hsp90 CTD inhibitors were discovered through virtual screening and protein fluorescence quenching assays, providing a potential avenue for developing new therapies using molecular chaperone inhibitors.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Dennis M. Bjorklund, R. Marc L. Morgan, Jasmeen Oberoi, Katie L. I. M. Day, Panagiota A. Galliou, Chrisostomos Prodromou
Summary: The study identified the interaction between CDC37 and BRAF and determined the crucial structural elements of CDC37 involved in BRAF recognition. The dimerization of BRAF can inhibit the recognition by CDC37, and the consequences of BRAF mutations on signaling were discussed.
Article
Biochemistry & Molecular Biology
Tahmina Akter, Hitoshi Nakamoto
Summary: Cyanobacterial chaperonins exhibit pH-dependent anti-aggregation activity, indicating potential regulation of chaperone function by pH changes during the light-dark cycle. Hsp90 and Hsp70 from Synechococcus elongatus PCC 7942 also display pH-dependent activities, with pH affecting their anti-aggregation and ATPase activities. Overall, an increase in pH enhances the activities of both chaperones in protein folding assistance.
JOURNAL OF BIOCHEMISTRY
(2021)
Article
Cell Biology
Huazhi Zhang, Zhihui Cui, Du Cheng, Yanyun Du, Xiaoli Guo, Ru Gao, Jianwen Chen, Wanwei Sun, Ruirui He, Xiaojian Ma, Qianwen Peng, Bradley N. Martin, Wei Yan, Yueguang Rong, Chenhui Wang
Summary: The gene RNF186 has been identified in genome-wide association studies as a susceptibility gene for ulcerative colitis, and it plays a crucial role in autophagy activation in colonic epithelial cells and intestinal homeostasis by regulating the ubiquitination of EPHB2. The absence of RNF186 and EPHB2 leads to a more severe phenotype in a colitis model, while treatment with ephrin-B1-Fc recombinant protein shows promise as a potential therapy for inflammatory bowel diseases.
Article
Immunology
Wanwei Sun, Heping Wang, Huijun Hu, Xiaojian Ma, Huazhi Zhang, Jianwen Chen, Yanyun Du, Ruirui He, Zhihui Cui, Qianwen Peng, Chenhui Wang
Summary: This study demonstrates that EPHB2 acts as a coreceptor for Dectin-1 ligand recognition and plays an essential role in antifungal immunity by phosphorylating Syk.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Ruirui He, Songfang Wu, Ru Gao, Jianwen Chen, Qianwen Peng, Huijun Hu, Liwen Zhu, Yanyun Du, Wanwei Sun, Xiaojian Ma, Huazhi Zhang, Zhihui Cui, Heping Wang, Bradley N. Martin, Yueying Wang, Cun-Jin Zhang, Chenhui Wang
Summary: The study showed that TRAF3IP2-AS1 regulates IL-17A signaling by recruiting SRSF10, indicating a therapeutic potential for IL-17-related autoimmune diseases.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Microbiology
Rui Guo, Xingyu Yan, Yanhua Li, Jin Cui, Saurav Misra, Andrew E. Firth, Eric J. Snijder, Ying Fang
Summary: This study demonstrates that PRRSV nsp2TF interacts with the major arteriviral envelope proteins GP5 and M, promoting arterivirus assembly by antagonizing ubiquitination-dependent proteasomal degradation of these key viral structural proteins.
Article
Multidisciplinary Sciences
Wanwei Sun, Xiaojian Ma, Heping Wang, Yanyun Du, Jianwen Chen, Huijun Hu, Ru Gao, Ruirui He, Qianwen Peng, Zhihui Cui, Huazhi Zhang, Junhan Wang, Xinming Jia, Bradley N. Martin, Cun-Jin Zhang, Xiaoxia Li, Chenhui Wang
Summary: Opportunistic fungal infections are a leading cause of death among immunocompromised patients, with MYO1F playing a key role in promoting antifungal immunity by regulating alpha-tubulin acetylation. Sirt2 deacetylase inhibitors show potential as drugs for the treatment of fungal infections, increasing the expression of proinflammatory genes and providing protection against Candida albicans infections.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Xiaojian Ma, Xi Tan, Bingbing Yu, Wanwei Sun, Heping Wang, Huijun Hu, Yanyun Du, Ruirui He, Ru Gao, Qianwen Peng, Zhihui Cui, Ting Pan, Xiong Feng, Junhan Wang, Chengqi Xu, Bin Zhu, Wei Liu, Chenhui Wang
Summary: Fungal infections cause millions of deaths each year and the mortality rate of disseminated candidiasis exceeds that of breast cancer and malaria. This study reveals the critical role of DOCK2 in promoting antifungal immune response and inflammation. DOCK2-deficient macrophages show reduced ability to kill intracellular fungi and activate downstream signaling pathways. Furthermore, nanoparticle-mediated delivery of IVT Rac1 mRNA enhances Rac1 activity and helps eliminate fungal infections in vivo.
CELLULAR & MOLECULAR IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yanyun Du, Qianwen Peng, Du Cheng, Ting Pan, Wanwei Sun, Heping Wang, Xiaojian Ma, Ruirui He, Huazhi Zhang, Zhihui Cui, Xiong Feng, Zhiqiang Liu, Tianxin Zhao, Wenjun Hu, Lei Shen, Wenyang Jiang, Na Gao, Bradley N. Martin, Cun-Jin Zhang, Zhanguo Zhang, Chenhui Wang
Summary: This study reveals that BTNL2 is a potent suppressor of anti-tumor immune response. Blockade of BTNL2 attenuates tumor progression and prolongs survival in tumor-bearing mice. BTNL2 interacts with γ δ T cell populations to promote IL-17A production, leading to a dysfunctional tumor immune microenvironment. High BTNL2 expression is associated with tumor types and negatively correlates with patient survival.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Lishu Chen, Chao Zhou, Qi Chen, Jingzhe Shang, Zhaodan Liu, Yan Guo, Chunfeng Li, HongJiang Wang, Qing Ye, XiaoFeng Li, Shulong Zu, Fangye Li, Qing Xia, Tao Zhou, Ailing Li, Chenhui Wang, Yun Chen, Aiping Wu, Chengfeng Qin, Jianghong Man
Summary: Zika virus treatment can enhance immune cell infiltration and activation in glioblastoma and inhibit tumor growth. Additionally, Zika virus can activate the interferon signaling pathway in glioblastoma cells. This therapy can improve the sensitivity of glioblastoma to immune checkpoint blockade.
MOLECULAR THERAPY-ONCOLYTICS
(2022)
Article
Biochemistry & Molecular Biology
Qianwen Peng, Ting Pan, Ruirui He, Ming Yi, Lingyun Feng, Zhihui Cui, Ru Gao, Heping Wang, Xiong Feng, Hui Li, Yuan Wang, Cun-jin Zhang, Du Cheng, Yanyun Du, Chenhui Wang
Summary: This study reveals that BTNL2 is necessary for colorectal IL-22 production and its knockout leads to decreased colonic tumorigenesis and more severe colitis phenotypes. BTNL2 acts on ILC3s, CD4(+) T cells, and gamma delta T cells to promote IL-22 production. Importantly, a monoclonal antibody against BTNL2 attenuates colorectal tumorigenesis in mice and mBTNL2-Fc recombinant protein shows therapeutic effect in a colitis model. This study not only identifies a regulatory mechanism of IL-22 production in the colorectal system, but also provides a potential therapeutic target for human colorectal cancer and inflammatory bowel diseases.
Article
Microbiology
Ruirui He, Jianwen Chen, Ziyan Zhao, Changping Shi, Yanyun Du, Ming Yi, Lingyun Feng, Qianwen Peng, Zhihui Cui, Ru Gao, Heping Wang, Yi Huang, Zhi Liu, Chenhui Wang
Summary: Recent research has found that common variants of the T-cell activation Rho GTPase-activating protein (TAGAP) are associated with susceptibility to inflammatory bowel diseases (IBDs) in humans, but the underlying mechanisms are still unclear. This study showed that TAGAP deficiency or downregulation of TAGAP expression caused by TAGAP gene polymorphism leads to decreased production of antimicrobial peptides (AMPs), such as reg3g, which in turn disrupts the gut microbiota, including Akkermansia muciniphila and Bacteroides acidifaciens strains. These strains can polarize T helper cell differentiation in the gut and exacerbate the phenotype of dextran sodium sulfate-induced disease in mice. Importantly, the study demonstrated that recombinant reg3g protein or anti-p40 monoclonal antibody had therapeutic effects in the treatment of dextran sodium sulfate-induced colitis, suggesting their potential as medicines for human IBD treatment, especially for patients carrying the common variant of TAGAP rs212388.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Immunology
Runjing Cao, Zihao Li, Chuyu Wu, Senlin Ji, Yahui Li, Xiang Cao, Xiaohong Dong, Meiling Jiang, Tao Pang, Chenhui Wang, Jingwei Li, Yun Xu, Cun-Jin Zhang
Summary: Pyroptosis is a key inflammatory form of cell death that plays an important role in the progression of many inflammatory diseases. In this study, we conducted a screening of compounds based on in silico docking and found that C202-2729 could significantly attenuate the severity of experimental autoimmune encephalomyelitis (EAE) and showed comparable effects to the clinical drug teriflunomide. Furthermore, we found that C202-2729 did not affect GSDMD cleavage, upstream inflammasome activation, pore formation, and mature IL-1b release in mouse macrophages. These findings suggest that C202-2729 may have potential for translational application in GSDMD-associated inflammatory diseases.
JOURNAL OF IMMUNOLOGY
(2022)
