Article
Multidisciplinary Sciences
Neharika Chamachi, Andreas Hartmann, Mai Quynh Ma, Anna Svirina, Georg Krainer, Michael Schlierf
Summary: This study investigates the essential role of periplasmic chaperones, 17-kilodalton protein (Skp) and survival factor A (SurA), in outer membrane protein (OMP) biogenesis. The researchers use single-molecule fluorescence spectroscopy to analyze the conformational dynamics and thermodynamics of Skp and SurA binding to unfolded OmpX and study their disaggre-gase activities. The findings provide insights into the multifaceted functionalities of Skp and SurA and shed light on the balance between conformational flexibility and underlying ener-getics in aiding chaperone action during OMP biogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Hao Geng, Yu-chen Pan, Ran Zhang, Dong Gao, Zijuan Wang, Boying Li, Ning Li, Dong-sheng Guo, Chengfen Xing
Summary: The excess accumulation of amyloid-beta (A beta) protein in the brain is the primary cause of Alzheimer's disease (AD). Inhibition of A beta fibrillation and disaggregation of A beta fibrils using near infrared (NIR) light-responsive nanoparticles (NPs) shows promising therapeutic potential for AD.
ADVANCED FUNCTIONAL MATERIALS
(2021)
Article
Biochemistry & Molecular Biology
Elisabete Ferreira, Zaida L. Almeida, Pedro F. Cruz, Marta Sousa, Paula Verissimo, Rui M. M. Brito
Summary: Several degenerative amyloid diseases have no effective treatment and are associated with the formation of protein aggregates and insoluble amyloid fibrils. Developing a reliable and economic screening protocol to identify potential fibril disruptors is important for finding new therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Xiaojing Sui, Dezerae Cox, Shuai Nie, Gavin E. Reid, Danny M. Hatters
Summary: During the recovery from heat shock, eukaryotic cells rapidly down-regulate prefoldins and translation machinery, while mobilizing protein quality control mechanisms, changing cellular energy metabolism, translational activity, and actin cytoskeleton. Long-term adaptation to stress involves the renewal of core cellular components.
JOURNAL OF PROTEOME RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Nina Kurokawa, Rio Midorikawa, Manami Nakamura, Keiichi Noguchi, Ken Morishima, Rintaro Inoue, Masaaki Sugiyama, Masafumi Yohda
Summary: The study examined the oligomeric structural change of CgHspB1 using sedimentation velocity analytical ultracentrifugation. It was found that at low temperatures, CgHspB1 exists as an 18-mer and is relatively unstable, partially dissociating into smaller oligomers. At elevated temperatures, the 24-mer is more stable and in dynamic equilibrium with the dissociated oligomers in the hexameric unit. Additionally, the disulfide bond between conserved cysteine residues plays a role in stabilizing the hexamers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Yumeng Yan, Sheng-You Huang
Summary: DeepHomo, a deep learning model for predicting inter-protein residue-residue contacts, integrates various information sources and achieves high precision, outperforming existing methods on both experimentally determined structures and simulated targets.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Wei-Chun Huang, Wai-Ting Chen, Yueh-Chen Chen, Shiuh-Bin Fang, Tzu-Wen Huang, Pei-Ru Chang, Yu-Chu Chang
Summary: Protein oligomerization is crucial for the pathogenesis of Salmonella Typhimurium. YqiC forms a homotrimer and its mutations result in reduced colonization and invasion to host cells. It interacts with subunits of the electron transport chain and ATP synthase, suggesting its role in energy modulation and virulence factor assembly.
Article
Chemistry, Multidisciplinary
Eunju Nam, Yuxi Lin, Jiyong Park, Hyunsu Do, Jiyeon Han, Bohyeon Jeong, Subin Park, Da Yong Lee, Mingeun Kim, Jinju Han, Mu-Hyun Baik, Young-Ho Lee, Mi Hee Lim
Summary: This study reveals that the interaction between APP-C31 and Aβ40 peptides promotes the aggregation and toxicity of Aβ40, leading to nuclear damage, neurite degeneration, and inflammation. This finding may offer a novel target for developing treatments for AD.
Article
Biochemistry & Molecular Biology
Shifeng Xiao, Qiuping Wu, Xuanbao Yao, Jiahao Zhang, Weicong Zhong, Junyi Zhao, Qiong Liu, Mohan Zhang
Summary: Isobavachalcone is a promising compound for potential preventive and therapeutic medicine for Alzheimer's disease, as it can inhibit tau protein aggregation and disaggregation, as well as regulate tau phosphorylation.
ACS CHEMICAL NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Christopher Sun, Leah Slade, Prisca Mbonu, Hunter Ordner, Connor Mitchell, Matthew Mitchell, Fu-Cheng Liang
Summary: This study investigates the effect of a novel protein chaperone, cpSRP43, on Aβ aggregation. The results show that cpSRP43 can effectively prevent and reverse Aβ aggregation, keeping Aβ in the soluble monomeric form. This research may provide new insights for the treatment of Alzheimer's disease.
Article
Biochemical Research Methods
Zhourun Wu, Qing Liao, Bin Liu
Summary: Protein complexes are key units for studying a cell system, and high-throughput approaches have enabled the determination of PPI data. The proposed mutual important interacting partner relation and the new algorithm idenPC-MIIP show improved performance in identifying protein complexes compared to existing methods.
BRIEFINGS IN BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Raliat O. Abioye, Ogadimma D. Okagu, Chibuike C. Udenigwe
Summary: In this study, three tetrapeptides (TNGQ, MANT, and YMSV) were identified as inhibitors of IAPP fibrillation. Among them, TNGQ was the most effective inhibitor. Through a series of experiments and molecular docking simulation, we revealed the mechanism of TNGQ in inhibiting IAPP fibrillation and found that TNGQ may act by disaggregating preformed IAPP fibrils.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sucharita Dey, Emmanuel D. Levy
Summary: An accurate understanding of protein quaternary structure is crucial for studying biomolecular mechanisms and diseases. By comparing structures and compositions of hetero-oligomers, using QS conservation across homologs, the study annotates complexes with a high accuracy exceeding 94%. The research provides high-quality annotations and a large benchmark dataset for hetero-assemblies.
Review
Biochemistry & Molecular Biology
Chuli Song, Tianyu Zhang, Yingjiu Zhang
Summary: Soluble aggregation and deposition of A beta 42 are the initial pathological hallmarks of Alzheimer's disease. Anti-A beta 42 antibodies can inhibit the aggregation and toxicity of A beta 42, but their epitope specificity affects their binding affinity for different A beta 42 species.
Article
Biochemistry & Molecular Biology
Olga N. Makshakova, Liliya R. Bogdanova, Dzhigangir A. Faizullin, Elena A. Ermakova, Yuriy F. Zuev
Summary: This study demonstrates the potential of sulfated polysaccharides as natural assistants in restoring damaged protein structures, particularly in eliminating cross-beta structures associated with amyloid fibrils. The effects of different types of polysaccharides on protein secondary structure conversion vary depending on their conformation and charge distribution along the chain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Md Mehedi Hassan, Shirina Sharmin, Hyeon-Jin Kim, Seong-Tshool Hong
Summary: HtrA1 and HtrA2/Omi proteins have been identified as plasmin-independent and highly specific thrombolytics that can dissolve intravascular thrombi specifically without causing bleeding risk. This study provides HtrA1 and HtrA2/Omi as ideal therapeutic candidates for various thrombotic diseases without hemorrhagic complications.
CIRCULATION RESEARCH
(2021)
Correction
Cell Biology
Ayse Ertay, Huiquan Liu, Dian Liu, Ping Peng, Charlotte Hill, Hua Xiong, David Hancock, Xianglin Yuan, Marcin R. Przewloka, Mark Coldwell, Michael Howell, Paul Skipp, Rob M. Ewing, Julian Downward, Yihua Wang
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Tereza Vaclova, Ursula Grazini, Lewis Ward, Daniel O'Neill, Aleksandra Markovets, Xiangning Huang, Juliann Chmielecki, Ryan Hartmaier, Kenneth S. Thress, Paul D. Smith, J. Carl Barrett, Julian Downward, Elza C. de Bruin
Summary: T790M subclonality is associated with poorer response to osimertinib and shorter progression-free survival, likely due to co-occurring PIK3CA alterations which can be targeted by PI3K pathway inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Yilu Zhou, Charlotte Hill, Liudi Yao, Juanjuan Li, David Hancock, Julian Downward, Mark G. Jones, Donna E. Davies, Rob M. Ewing, Paul Skipp, Yihua Wang
Summary: Alveolar type II (ATII) epithelial cells function as stem cells and are crucial for alveolar renewal, repair, and cancer. Research has shown that RAS activation induces epithelial-mesenchymal transition (EMT), while activation of the TGF-beta signaling pathway alone only induces partial EMT.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Genetics & Heredity
Satyamaanasa Polubothu, Davide Zecchin, Lara Al-Olabi, Daniel A. Lionarons, Mark Harland, Stuart Horswell, Anna C. Thomas, Lilian Hunt, Nathan Wlodarchak, Paula Aguilera, Sarah Brand, Dale Bryant, Cristina Carrera, Hui Chen, Greg Elgar, Catherine A. Harwood, Michael Howell, Lionel Larue, Sam Loughlin, Jeff MacDonald, Josep Malvehy, Sara Martin Barberan, Vanessa Martins da Silva, Miriam Molina, Deborah Morrogh, Dale Moulding, Jeremie Nsengimana, Alan Pittman, Juan-Anton Puig-Butille, Kiran Parmar, Neil J. Sebire, Stephen Scherer, Paulina Stadnik, Philip Stanier, Gemma Tell, Regula Waelchli, Mehdi Zarrei, Susana Puig, Veronique Bataille, Yongna Xing, Eugene Healy, Gudrun E. Moore, Wei-Li Di, Julia Newton-Bishop, Julian Downward, Veronica A. Kinsler
Summary: This study identified a previously unreported genetic susceptibility to melanoma and melanocytic nevi, familial duplications of gene PPP2R3B. Duplications of this gene increase the expression of PR70 in human nevus and melanoma tissue, affecting survival through a nonimmunological mechanism. Overexpression of PPP2R3B induces pigment cell switching toward proliferation and away from migration, driven by C21orf91 independent of the known MITF-controlled switch. This work confirms the power of a rare disease approach and identifies C21orf91 as a potentially targetable hub in controlling phenotype switching.
GENETICS IN MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Liudi Yao, Yilu Zhou, Juanjuan Li, Leanne Wickens, Franco Conforti, Anna Rattu, Fathima Maneesha Ibrahim, Aiman Alzetani, Ben G. Marshall, Sophie Fletcher, David Hancock, Tim Wallis, Julian Downward, Rob M. Ewing, Luca Richeldi, Paul Skipp, Donna E. Davies, Mark G. Jones, Yihua Wang
Summary: The study identified aberrant bidirectional epithelial-mesenchymal crosstalk in IPF, forming a chronic feedback loop that maintains profibrotic signals.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Stelios Chrysostomou, Rajat Roy, Filippo Prischi, Lucksamon Thamlikitkul, Kathryn L. Chapman, Uwais Mufti, Robert Peach, Laifeng Ding, David Hancock, Christopher Moore, Miriam Molina-Arcas, Francesco Mauri, David J. Pinato, Joel M. Abrahams, Silvia Ottaviani, Leandro Castellano, Georgios Giamas, Jennifer Pascoe, Devmini Moonamale, Sarah Pirrie, Claire Gaunt, Lucinda Billingham, Neil M. Steven, Michael Cullen, David Hrouda, Mathias Winkler, John Post, Philip Cohen, Seth J. Salpeter, Vered Bar, Adi Zundelevich, Shay Golan, Dan Leibovici, Romain Lara, David R. Klug, Sophia N. Yaliraki, Mauricio Barahona, Yulan Wang, Julian Downward, J. Mark Skehel, Maruf M. U. Ali, Michael J. Seckl, Olivier E. Pardo
Summary: The study identified RSK4 as a driver of drug resistance and metastasis in lung and bladder cancer cells, and silencing this kinase increased sensitivity to chemotherapy and reduced metastasis. Drug screening revealed fluoroquinolone antibiotics as potent RSK4 inhibitors, with trovafloxacin replicating effects of RSK4 silencing. Further structural analysis provided insights into how trovafloxacin blocks RSK4 kinase activation. Additionally, patients receiving chemotherapy and prophylactic levofloxacin showed significantly prolonged overall survival, suggesting RSK4 inhibition as a potential therapeutic strategy for lung and bladder cancer.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Tereza Vaclova, Atanu Chakraborty, James Sherwood, Sarah Ross, Danielle Carroll, J. Carl Barrett, Julian Downward, Elza C. de Bruin
Summary: The study investigates the co-occurrence of additional KRAS mutations with KRAS G12C in non-small cell lung cancer (NSCLC) tumors and its impact on cellular response to G12C-specific inhibitors. The results show that KRAS c.35G>T mutation most frequently co-occurred with KRAS G12C and led to cellular resistance to G12C inhibitors. Therefore, comprehensive genotyping of KRAS tumors is necessary for optimal patient selection for treatment with a KRAS G12C inhibitor.
SCIENTIFIC REPORTS
(2022)
Article
Microbiology
Enkhchimeg Lkhagva, Hea-Jong Chung, Ji-Seon Ahn, Seong-Tshool Hong
Summary: This study compared the impact of transitioning from a meatatarian diet to a vegetarian diet and engaging in physical exercise on the composition of the gut microbiome. The results showed that physical exercise had a more significant effect on the microbiome composition than diet transition, with differences in the patterns of change and diversity.
Article
Microbiology
Chongkai Zhai, Ji-Seon Ahn, Md Minarul Islam, Enkhchimeg Lkhagva, Hea-Jong Chung, Seong-Tshool Hong
Summary: This study analyzes the effects of gut microbiome on host phenotype by replacing the original gut microbiome with a new one within the same individual. The results show that different gut microbiomes have different effects on weight gain, and weight gain is negatively correlated with the Firmicutes/Bacteroidetes ratio.
Editorial Material
Medicine, General & Internal
Miriam Molina-Arcas, Julian Downward
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Multidisciplinary Sciences
Philip East, Gavin P. Kelly, Dhruva Biswas, Michaela Marani, David C. Hancock, Todd Creasy, Kris Sachsenmeier, Charles Swanton, Julian Downward, Sophie de Carne Trecesson
Summary: The study found that 84% of patients with lung adenocarcinoma have oncogenic activation of the RAS signaling pathway, with a high proportion of activation even in KRAS wild-type tumors; patient groups with high RAS activity show adverse clinical outcomes and reduced response to chemotherapy. Stratifying patients based on oncogenic RAS transcriptional activity may ultimately assist in clinical decision-making.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
May Zaw Thin, Christopher Moore, Thomas Snoeks, Tammy Kalber, Julian Downward, Axel Behrens
Summary: In this paper, a method of lung nodule image acquisition and analysis using a micro-computed tomography scanner is introduced for translational research in lung cancer that closely mimics clinical environments. The method has the advantages of low radiation dose, high resolution, and high-throughput imaging, and utilizes specific image analysis tools for identifying different types of lung tumors.
Article
Biochemistry & Molecular Biology
Ji-Seon Ahn, Yu-Jin Choi, Han-Byeol Kim, Hea-Jong Chung, Seong-Tshool Hong
Summary: This study demonstrates that the gut microbiome can contribute differently to locomotion and explains the mixed results in previous research on the association between the gut microbiome and locomotion.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Mst Ismat Ara Begum, Lin Chuan, Seong-Tshool Hong, Hee-Suk Chae
Summary: Association studies have shown that miRNA expression is significantly altered in relation to diseases, including endometriosis (EMS), particularly within inflammatory pathways. This article reviews the advancements made in understanding the pathological role of miRNA in EMS and its association with EMS-associated infertility, highlighting the potential for developing miRNA-based therapeutics and diagnostic markers.