Article
Biology
William N. Zagotta, Brandon S. Sim, Anthony K. Nhim, Marium M. Raza, Eric G. B. Evans, Yarra Venkatesh, Chloe M. Jones, Ryan A. Mehl, E. James Petersson, Sharona E. Gordon
Summary: With the recent explosion in high-resolution protein structures, there is a new frontier in biology to elucidate the mechanisms of conformational rearrangements in proteins to meet the changing needs of cells. By rigorously measuring protein energetics and dynamics through new methods like tmFRET, differences in conformational states and accurate quantification of distributions can be revealed. This new approach using Acd for time-resolved tmFRET sets the stage for measuring the energetics of conformational rearrangements in soluble and membrane proteins in near-native conditions.
Article
Biochemistry & Molecular Biology
Elodie Blondel-Tepaz, Marie Leverve, Badr Sokrat, Justine S. Paradis, Milena Kosic, Kusumika Saha, Cedric Auffray, Evelyne Lima-Fernandes, Alessia Zamborlini, Anne Poupon, Louis Gaboury, Jane Findlay, George S. Baillie, Herve Enslen, Michel Bouvier, Stephane Angers, Stefano Marullo, Mark G. H. Scott
Summary: The protein beta-arrestin2 plays a critical role in regulating the Mdm2-p53 signaling axis by promoting the nuclear-cytoplasmic shuttling of Mdm2 and enhancing p53 signaling. While beta-arrestin2 can be SUMOylated, it is the non-covalent interaction between SUMO and beta-arrestin2, mediated by a SUMO interaction motif (SIM), that is essential for its cytonuclear trafficking function. Depletion of the RanBP2/RanGAP1-SUMO nucleocytoplasmic transport hub leads to defective beta-arrestin2 nuclear entry, inhibiting its ability to displace Mdm2 from the nucleus and enhancing p53 signaling in cancer cells.
Article
Biochemistry & Molecular Biology
Rui Yin, Jiacheng Song, Aurora Esquela-Kerscher, Oliver Kerscher
Summary: This study demonstrates differences in SUMO levels and localization between normal and cancer cells in response to stress, indicating that cancer cells may exhibit an enhanced stress response. The enrichment of cytosolic SUMO in prostate cancer cell lines upon stress exposure, compared to normal cells, was reversible.
MOLECULAR CARCINOGENESIS
(2021)
Article
Biochemistry & Molecular Biology
Luyao Wei, Wantao Wang, Junxia Yao, Zhengyu Cui, Zihang Xu, Hanqing Ding, Xiaojun Wu, Deheng Wang, Jia Luo, Zun-Ji Ke
Summary: This study identifies protein activator of the interferon-induced protein kinase (PACT) as a key player in basal-like breast cancer (BLBC) metastasis. High expression of PACT is associated with poor prognosis in BLBC patients. It is found that PACT regulates BLBC metastasis by interacting with SUMO-conjugating enzyme Ubc9.
Article
Multidisciplinary Sciences
David Scheerer, Bharat V. Adkar, Sanchari Bhattacharyya, Dorit Levy, Marija Iljina, Inbal Riven, Orly Dym, Gilad Haran, Eugene I. Shakhnovich
Summary: Enzymes have a crucial role in controlling chemical reactions and achieving high catalytic efficiency and selectivity. The three-domain enzyme adenylate kinase (AK) catalyzes phosphotransfer between ATP and AMP. Our study using single-molecule FRET spectroscopy reveals that AMP inhibits AK by promoting faster and more cooperative domain closure by ATP, leading to an increased population of the closed state. We developed a model based on experimentally observed opening and closing rates, explaining the complex activity of AK, particularly substrate inhibition, and highlighting the importance of protein motions in enzymatic activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Biochemistry & Molecular Biology
Jiayu Liao, Vipul Madahar, Runrui Dang, Ling Jiang
Summary: Protein-protein interactions are vital in life, and FRET is widely used to detect molecular interactions with high sensitivity and efficiency. Attempts to develop FRET into a quantitative measurement for interaction affinity have faced challenges, but the method shows great potential for studying difficult-to-express proteins and interactions in living cells.
Review
Cell Biology
Hyunbin Kim, In-Yeop Baek, Jihye Seong
Summary: This review introduces genetically encoded fluorescent biosensors that can precisely monitor the real-time activation process of G protein-coupled receptors (GPCRs) in live cells. These sensors allow observation of the activation process of GPCRs, including the binding of extracellular ligands, conformational changes of GPCRs, recruitment of G proteins or beta-arrestin, internalization and trafficking of GPCRs, and downstream signaling events associated with GPCRs.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Brian Tenner, Jason Z. Zhang, Yonghoon Kwon, Veronica Pessino, Siyu Feng, Bo Huang, Sohum Mehta, Jin Zhang
Summary: FluoSTEPs is a novel class of biosensors that combines self-complementing split green fluorescent protein, CRISPR-mediated knock-in, and fluorescence resonance energy transfer technology to probe compartmentalized signaling dynamics in situ. It can simultaneously highlight endogenous microdomains and report domain-specific, real-time signaling events, including kinase activities, guanosine triphosphatase activation, and second messenger dynamics. FluoSTEPs have been shown to be useful in probing spatiotemporal regulation within endogenous signaling architectures, as demonstrated by a FluoSTEP for 3',5'-cyclic adenosine monophosphate (cAMP) revealing distinct cAMP dynamics within clathrin microdomains in response to stimulation of G protein-coupled receptors.
Article
Chemistry, Multidisciplinary
Khyati Gohil, Sheng-Yi Wu, Kei Takahashi-Yamashiro, Yi Shen, Robert E. Campbell
Summary: Genetically encoded biosensors based on Forster resonance energy transfer (FRET) are essential tools for monitoring biochemical changes in cells. Green and red fluorescent protein-based FRET pairs offer advantages over cyan and yellow fluorescent protein pairs, including better spectral separation, lower phototoxicity, and less autofluorescence. In this study, a green fluorescent protein called mWatermelon, derived from mScarlet, was developed and used as a FRET donor to mScarlet-I, a red fluorescent protein, as the FRET acceptor. The functionality of this FRET pair was tested by constructing biosensors for the detection of protease activity, Ca2+, and K+. Furthermore, a strategy to enhance the FRET efficiency of these biosensors by modulating the intramolecular association between mWatermelon and mScarlet-I was described.
Article
Biochemistry & Molecular Biology
A. Ro Han, Trishaladevi Durgannavar, Dohee Ahn, Sang J. Chung
Summary: This study demonstrated the use of a modified p73-TAD peptide for FRET-based assay of p73-TAD binding to MDM2, showing that Nutiln-3 can effectively compete for MDM2 binding. The developed FRET binding assay holds promise for screening novel drugs inhibiting interactions between p73 and MDM2.
Article
Biochemistry & Molecular Biology
Anne Susemihl, Felix Nagel, Piotr Grabarczyk, Christian A. Schmidt, Mihaela Delcea
Summary: Zinc finger proteins play important roles in various cellular processes, with BCL11B being a member of this protein family. A simple and fast protocol was described for preparing a fluorescently tagged protein for in vitro studies, which can be valuable for further research in understanding zinc finger domains.
Article
Biochemistry & Molecular Biology
Sandra Burgstaller, Helmut Bischof, Lucas Matt, Robert Lukowski
Summary: Cancer is a major cause of death globally, and understanding the molecular mechanisms behind the disease is crucial. Altered K+ channel expression is frequently associated with various types of cancer, impacting malignancy and disease outcomes. However, the precise roles of oncogenic K+ channels in cell physiology, homeostasis, and subcellular compartments are not well understood. Genetically encoded fluorescent biosensors provide a non-invasive approach to simultaneously investigate metabolic and ionic signaling in individual cells and organelles, allowing for a high-resolution study of compartmentalized metabolite or ion dynamics. These versatile tools have been used to visualize and understand the subcellular consequences of aberrant K+ channel expression and activity in K+ channel-related cancer research.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Jacob R. Pope, Rachel L. Johnson, W. David Jamieson, Harley L. Worthy, Senthilkumar Kailasam, Rochelle D. Ahmed, Ismail Taban, Husam Sabah Auhim, Daniel W. Watkins, Pierre J. Rizkallah, Oliver K. Castell, D. Dafydd Jones
Summary: Fluorescent proteins (FPs) are often used in pairs to monitor biomolecular events. GFP homodimers are brighter than monomers, while heterodimers typically have lower FRET efficiency than predicted.
Article
Chemistry, Analytical
Mehmet Yunus Genceroglu, Cansu Cavdar, Selen Manioglu, Halil Bayraktar
Summary: This study presents a genetically encoded fluorescence method for monitoring the conformational changes of Cytc upon binding to heme and CCHL. The results show that the noncovalent interaction of heme in the absence of CCHL induces a partially folded state of Cytc, while higher concentrations of heme and coexpression of CCHL lead to the recovery of Cytc native structure.
Article
Chemistry, Multidisciplinary
Vanessa Vongsouthi, Jason H. Whitfield, Petr Unichenko, Joshua A. Mitchell, Bjorn Breithausen, Olga Khersonsky, Leon Kremers, Harald Janovjak, Hiromu Monai, Hajime Hirase, Sarel J. Fleishman, Christian Henneberger, Colin J. Jackson
Summary: The study engineered a Dalanine-specific SBP into a fluorescence biosensor for the signaling molecule D-serine, enhancing affinity, specificity, thermostability, and dynamic range through binding site and remote mutations. This sensor allowed measurement of physiologically relevant changes in D-serine concentration.
Article
Nanoscience & Nanotechnology
Shih-Wei Chiu, An Hsu, Lei Ying, Yong-Kang Liaw, Kun-Ta Lin, Jrjeng Ruan, Ifor D. W. Samuel, Ben B. Y. Hsu
Summary: Researchers propose a solution to the challenge of charge transport imbalance in bilayer organic light-emitting field-effect transistors (OLEFETs) by introducing a specially designed transparent organic/inorganic hybrid contact. Numerical simulations show that this design can steadily accumulate electrons injected into the emissive polymer, allowing the light-emitting interface to effectively capture more holes even when the hole current increases.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Chemistry, Physical
Lin-jie Yang, Wenye Xuan, David Webster, Lethy Krishnan Jagadamma, Teng Li, David N. Miller, David B. Cordes, Alexandra M. Z. Slawin, Graham A. Turnbull, Ifor D. W. Samuel, Hsin-Yi Tiffany Chen, Philip Lightfoot, Matthew S. Dyer, Julia L. Payne
Summary: One of the advantages of organic-inorganic metal halides is their highly tuneable structures and properties, which are important for optimizing materials for photovoltaics and optoelectronic devices. In this study, bromine was included in a layered perovskite to induce a decrease in band gap and a structural transition. The inclusion of bromine also resulted in the formation of a new band in the electronic structure and a significant increase in mobility and/or carrier concentration. This work highlights the potential of molecular inclusion as a tool to tune the electronic properties of layered organic-inorganic perovskites.
CHEMISTRY OF MATERIALS
(2023)
Article
Chemistry, Inorganic & Nuclear
Hang Liu, Hassan Hafeez, David B. Cordes, Alexandra M. Z. Slawin, Gavin Peters, Stephen L. Lee, Ifor D. W. Samuel, Finlay D. Morrison
Summary: In this work, a novel inorganic halide Cs10MnSb6Cl30 with a distinctive 10H perovskite polytype structure is reported. The Cs10MnSb6Cl30 has 30% B-site vacancies ordered at both corner-and face-sharing sites, resulting in a reduction of octahedral connectivity to 1D and enhanced photoluminescence. This study demonstrates the existence of the 10H perovskite structure in halides and the potential of vacancy rearrangements to tune the optical properties of perovskite polytypes.
INORGANIC CHEMISTRY
(2023)
Article
Cell Biology
Ellis G. Jaffray, Michael H. Tatham, Barbara Mojsa, Magda Liczmanska, Alejandro Rojas-Fernandez, Yili Yin, Graeme Ball, Ronald T. Hay
Summary: Jaffray et al. demonstrated that the degradation of PML and PML-RARA induced by arsenic relies on the VCP/p97 segregase protein. Arsenic trioxide treatment leads to degradation of PML-RARA and PML, curing the disease. The UFD1-NPLOC4-p97 segregase complex is essential for extracting poly-ubiquitinated, poly-SUMOylated PML from PML bodies prior to proteasomal degradation.
JOURNAL OF CELL BIOLOGY
(2023)
Article
Chemistry, Physical
P. E. Brown, A. Ruseckas, L. K. Jagadamma, O. Blaszczyk, J. R. Harwell, N. Mica, E. Zysman-Colman, I. D. W. Samuel
Summary: Charge diffusion and extraction are important processes in solar cells. In this study, time-resolved photoluminescence was used to investigate electron diffusion and transfer in hybrid perovskite films. It was found that introducing a fullerene monolayer between the MAPbI3 and SnO2 layers significantly increased the electron transfer velocity, suggesting that electron diffusion limits the rate of charge extraction. These findings suggest that enhancing the electron diffusion coefficient in MAPbI3 could improve the efficiency of solar cells.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Oncology
Iago P. F. Nunes, Pedro J. L. Crugeira, Fernando J. P. Sampaio, Susana C. P. S. de Oliveira, Juliana M. Azevedo, Caio L. O. Santos, Luiz G. P. Soares, Ifor D. W. Samuel, Saydulla Persheyev, Paulo F. de Ameida, Antonio L. B. Pinheiro
Summary: This study aimed to evaluate the efficacy of photodynamic therapy (PDT) using dimethyl methylene blue zinc chloride double salt (DMMB) and red LED light on Candida albicans. The results showed that applying double PDT in a single session was the most effective approach for inhibiting the proliferation of Candida albicans.
PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY
(2023)
Article
Virology
Wing-Hang Ip, Michael H. Tatham, Steewen Krohne, Julia Gruhne, Michael Melling, Tina Meyer, Britta Gornott, Luca D. Bertzbach, Ronald T. Hay, Estefania Rodriguez, Thomas Dobner
Summary: This study used quantitative SUMO proteomics to analyze the cellular consequences of E1B-55K-mediated host cell modulation and adenovirus infection. The results showed that changes in the SUMOylated proteome could regulate DNA damage response, cell cycle control, chromatin assembly, and gene transcription. Additionally, a SUMO-dependent, ubiquitin-mediated degradation mechanism for some SUMO substrates was identified, suggesting that E1B-55K might use multiple mechanisms to alter restrictive cellular pathways.
JOURNAL OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Emil P. T. Hertz, Ignacio Alonso-de Vega, Thomas Kruse, Yiqing Wang, Ivo A. Hendriks, Anna H. Bizard, Ania Eugui-Anta, Ronald T. Hay, Michael L. Nielsen, Jakob Nilsson, Ian D. Hickson, Niels Mailand
Summary: Hertz et al. use CRISPR screening to identify genetic vulnerabilities to inhibition of SUMOylation in human cells. They show that SUMO exerts its essential role in cell proliferation via NIP45- and BTRR-PICH-mediated DNA catenane resolution pathways. NIP45 mediates a TOP2-independent DNA catenane resolution process through its SUMO-like domains, promoting SUMOylation of specific factors including the SLX4 multi-nuclease complex, which contributes to catenane conversion into DSBs. Their findings establish the importance of SUMOylation in enabling resolution of toxic DNA catenanes via non-epistatic NIP45- and BTRR-PICH-dependent pathways to prevent mitotic failure.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biology
Sofie E. Voerman, Beauregard C. Marsh, Ricardo G. Bahia, Guilherme H. Pereira-Filho, Ana Clara F. Becker, Gilberto M. Amado-Filho, Arvydas Ruseckas, Graham A. Turnbull, Ifor D. W. Samuel, Heidi L. Burdett
Summary: Investigated the photo- and chromatic acclimation and morphological change of red coralline algae in mesophotic depths. Results showed that these algae can maintain photosynthetic function under decreasing light intensity and spectral availability, but this leads to smaller and less complex thalli. The photo-acclimatory response is conserved at least at the Order level, while chromatic acclimation is not depth-dependent. Use of photoprotection is necessary at 65 m depth, while optimal light levels are met at 86 m.
PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Marta Piksa, Wojciech Fortuna, Cheng Lian, Malgorzata Gacka, Ifor D. W. Samuel, Katarzyna Matczyszyn, Krzysztof J. Pawlik
Summary: We evaluated the efficacy of antimicrobial Photodynamic Therapy (APDT) using organic light-emitting diodes (OLED) for antibiotic-resistant clinical strains from diabetic foot ulcers. The isolated strains from diabetic foot ulcers were identified and tested for antibiotic susceptibility. APDT using OLED as a light source and methylene blue as a photosensitizer effectively reduced pathogens and opportunistic bacteria regardless of drug resistance.
SCIENTIFIC REPORTS
(2023)
Article
Cell Biology
Magda Liczmanska, Michael H. Tatham, Barbara Mojsa, Ania Eugui-Anta, Alejandro Rojas-Fernandez, Adel F. M. Ibrahim, Ronald T. Hay
Summary: The small ubiquitin-like modifier (SUMO) protease SENP6 disassembles SUMO chains from cellular substrate proteins. Proteins of the lamin family show increased SUMO modification after SENP6 depletion, accompanied by nuclear structural changes similar to laminopathies. Proximity-induced SUMO modification (PISM) directly targets lamin A/C for SUMO conjugation, recapitulating altered nuclear structure after SENP6 depletion. SENP6 activity protects the nucleus against hyperSUMOylation-induced laminopathy-like alterations.
Article
Nanoscience & Nanotechnology
Jonathon Harwell, Ifor D. W. Samuel
Summary: This study demonstrates the use of nanoimprint lithography to fabricate honeycomb-shaped, quasi-interdigitated electrode structures for back-contact perovskite solar cells. The efficiency of the resulting devices remains almost unchanged as the electrode width is varied from 230 to 2000 nm, suggesting that improving the quality of charge transport layers and reducing recombination are more important for maximizing the performance of these solar cells than reducing the minimum feature size.
ACS APPLIED NANO MATERIALS
(2023)
Review
Chemistry, Multidisciplinary
Marta Piksa, Cheng Lian, Imogen C. Samuel, Krzysztof J. Pawlik, Ifor D. W. Samuel, Katarzyna Matczyszyn
Summary: Antimicrobial photodynamic therapy (APDT) is a promising approach to combat antimicrobial resistance by using light to activate chemicals that generate reactive oxygen species. While studies have shown its efficacy against various microorganisms, the role of light and the choice of light source have been overlooked, hindering its application in clinical settings.
CHEMICAL SOCIETY REVIEWS
(2023)
Article
Chemistry, Physical
John Marques Dos Santos, Lethy Krishnan Jagadamma, Michele Cariello, Ifor D. W. Samuel, Graeme Cooke
Summary: BODIPY-based materials, known for their stability and tunability, are promising hole transporting materials (HTMs) for perovskite solar cells (PSCs). In this study, a new BODIPY molecule, PTZ-PTZ-BDP, functionalized with phenothiazine moieties, was synthesized and evaluated as an HTM. The results showed that PTZ-PTZ-BDP had suitable energy levels and reversible redox processes. PSCs using PTZ-PTZ-BDP as the HTM demonstrated a champion power conversion efficiency of 14.6% and comparable stability to state-of-the-art HTMs, indicating the potential of BODIPY-based HTMs in PSCs.
SUSTAINABLE ENERGY & FUELS
(2022)