Article
Multidisciplinary Sciences
Michael J. Roy, Minglyanna G. Surudoi, Ashleigh Kropp, Jianmei Hou, Weiwen Dai, Joshua M. Hardy, Lung-Yu Liang, Thomas R. Cotton, Bernhard C. Lechtenberg, Toby A. Dite, Xiuquan Ma, Roger J. Daly, Onisha Patel, Isabelle S. Lucet
Summary: PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. The researchers elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. They identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2.
NATURE COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Sathapana Kongsamut, Haifeng Eishingdrelo
Summary: The activation of G-protein-coupled receptors (GPCRs) triggers a cascade of reactions, including changes in receptor structures, phosphorylation, protein recruitment, trafficking and gene expression. Two well-studied signaling pathways of GPCRs are G-protein-mediated and arrestin-mediated pathways. Recently, interactions between GPCRs and 14-3-3 proteins have been discovered, which opens new possibilities in signal transduction. 14-3-3 proteins are crucial for GPCR trafficking and signal transduction, providing potential for studying GPCR function and therapeutics.
DRUG DISCOVERY TODAY
(2023)
Article
Biology
Pavel Pohl, Rohit Joshi, Olivia Petrvalska, Tomas Obsil, Veronika Obsilova
Summary: The study investigated the structural basis of Nedd4-2 regulation by 14-3-3 and identified phosphorylated Ser342 and Ser448 as key residues facilitating 14-3-3 binding. The Nedd4-2:14-3-3 complex induces a structural rearrangement of Nedd4-2 by inhibiting interactions between its structured domains.
COMMUNICATIONS BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Bence Feher, Judith Mihaly, Attila Demeter, Laszlo Almasy, Andras Wacha, Zoltan Varga, Imre Varga, Jan Skov Pedersen, Attila Bota
Summary: The red-emitting fluorescent properties of BSA-gold conjugates are attributed to loose ionic gold-protein complexes rather than gold nanoclusters. The behavior of fluorescence and structure in normal and heavy water differ, with a higher quantum yield for red-emitting luminescence in heavy water. Changes in red luminescence are associated with perturbations in protein conformations and alterations to gold-sulfur and gold-oxygen interactions.
Article
Pharmacology & Pharmacy
Claire C. Munier, Christian Ottmann, Matthew W. D. Perry
Summary: The 14-3-3 proteins play crucial roles in regulating the inflammatory response at genetic, molecular, and cellular levels. They affect key components of the immune response and can lead to clinical syndromes when their recognition processes are disrupted. Abnormal levels of 14-3-3 contribute to undesirable immune responses and chronic inflammatory conditions.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Lea Reuter, Tanja Schmidt, Prabha Manishankar, Christian Throm, Jutta Keicher, Andrea Bock, Irina Droste-Borel, Claudia Oecking
Summary: NPH3 plays a crucial role in auxin-dependent plant phototropism, with blue light triggering its dissociation from the plasma membrane through phosphorylation and interaction with 14-3-3 proteins. In darkness, NPH3 binds polyacidic phospholipids for membrane association. The dynamic change in NPH3 localization mediated by 14-3-3 is essential for auxin-dependent phototropism.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Bente A. Somsen, Fenna W. B. Craenmehr, Wei-Hong W. Liu, Auke A. Koops, Marloes A. M. Pennings, Emira J. Visser, Christian Ottmann, Peter J. Cossar, Luc Brunsveld
Summary: Molecular glues represent a novel approach in drug discovery, however, the targeted stabilization of protein complexes is still challenging due to a lack of drug design rules. This study demonstrates the successful development of a peptide-based molecular glue that selectively stabilizes the 14-3-3/ChREBP protein-protein interaction by utilizing the functional mapping of hotspots.
Article
Chemistry, Analytical
Yulong Jin, Kun Xu, Yanyan Huang, Huifei Zhong, Rui Zhao
Summary: The newly developed cell-permeable fluorescent probe can selectively exhibit a ratiometric response towards the apoptotic key enzyme caspase-3, offering potential for real-time quantification of caspase-3 activity to estimate apoptotic stages in living cells.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yifan Lu, Gayani Nanayakkara, Yu Sun, Lu Liu, Keman Xu, Charles Drummer, Ying Shao, Fatma Saaoud, Eric T. Choi, Xiaohua Jiang, Hong Wang, Xiaofeng Yang
Summary: LPC induces nuclear localization of pro-caspase-1 in HAECs, where it can re-export to the cytosol through specific mechanisms. Combination of LPC with NES inhibitor promotes inflammatory gene expression, triggering inflammation through different pathways.
Article
Biochemistry & Molecular Biology
Chang-Heng Hsieh, Chia-Cheng Chou, Ya-Ching Fang, Po-Hao Hsu, Yi-Hung Chiu, Chi-Sheng Yang, Guey-Mei Jow, Chih-Yung Tang, Chung-Jiuan Jeng
Summary: Endogenous 14-3-3 proteins play a chaperone-like role in regulating the stability of Eag1 protein and modulators of 14-3-3 have therapeutic potential in correcting protein expression of disease-causing Eag1 mutants.
CELL AND BIOSCIENCE
(2023)
Article
Cell Biology
Yuan Huang, Shi Li, Qinfeng Liu, Zhijie Wang, Shunyao Li, Lei Liu, Weiwei Zhao, Kai Wang, Rui Zhang, Longfei Wang, Ming Wang, Declan William Ali, Marek Michalak, Xing-Zhen Chen, Cefan Zhou, Jingfeng Tang
Summary: This study reveals that lymphocyte-specific protein tyrosine kinase (LCK) directly interacts with transient receptor potential melastatin 8 (TRPM8) and enhances its phosphorylation at Y1022. LCK positively regulates TRPM8 channel function by increasing TRPM8 multimerization. Additionally, the interaction between TRPM8 and 14-3-3 zeta positively modulates channel multimerization. The phosphorylation of TRPM8 at Y1022 plays a crucial role in the proliferation, migration, and tumorigenesis of pancreatic cancer cells.
CELL DEATH & DISEASE
(2022)
Article
Chemistry, Multidisciplinary
Stephen I. Ting, Dylan W. Snelson, Tucker R. Huffman, Akihiro Kuroo, Ryota Sato, Ryan A. Shenvi
Summary: Researchers have reported a concise synthesis of (-)-cotylenol via a 10-step asymmetric entry. This route features a reaction that tolerates steric hindrance and a tandem reaction that establishes an 8-membered ring. The method sets the stage for focused library synthesis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Analytical
Qian Lei, Xueyan Huang, Lijuan Zheng, Fan Zheng, Jie Dong, Fei Chen, Wenbin Zeng
Summary: Caspase-3 plays a crucial role in apoptosis and related diseases. Detecting Caspase-3 is important for apoptosis imaging and evaluating the effectiveness of early tumor treatment. This article systematically summarizes recent innovations in Caspase-3 responsive fluorescence biosensors, discussing the performance of various luminescence probes in Caspase-3 detection.
Article
Spectroscopy
Xiaoyuan Ma, Jingna Zhang, Zhouping Wang
Summary: The study focused on real-time detection of caspase 3 in living cells using a dual-mode nanosensor based on SERS-fluorescence. The sensor showed good linear relationship between caspase 3 and both SERS and fluorescence signals, with a minimum detection limit of 0.001 nM. Activation of caspase 3 was observed in cells stimulated by AFB1, providing detailed information for apoptosis monitoring.
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
(2021)
Article
Biochemistry & Molecular Biology
Hetao Chen, Hang Zhang, Pu Chen, Song Xiang
Summary: This study elucidated the interaction mechanism between CRTCs and 14-3-3, as well as their crucial roles in nuclear translocation and activation of gene transcription. The discovery of a novel salt bridge structure expanded the understanding of this interaction.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biophysics
Rohit Joshi, Pavel Pohl, Dita Strachotova, Petr Herman, Tomas Obsil, Veronika Obsilova
Summary: Nedd4-2, a ubiquitin ligase, is involved in the endocytosis and degradation of target molecules through interactions with 14-3-3 proteins. The binding of 14-3-3 induces structural rearrangement of Nedd4-2, affecting the mobility and emission properties of certain domains. In contrast, the active site of the HECT domain becomes more mobile upon 14-3-3 binding.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Kristyna Bousova, Monika Zouharova, Petr Herman, Jiri Vymetal, Veronika Vetyskova, Katerina Jiraskova, Jiri Vondrasek
Summary: In this study, we found that the N-terminus of TRPM5 interacts with calcium-binding proteins CaM and S100A1, and these binding regions possess unique basic residues.
Article
Biochemistry & Molecular Biology
Raju Mandal, Klara Kohoutova, Olivia Petrvalska, Matej Horvath, Pavel Srb, Vaclav Veverka, Veronika Obsilova, Tomas Obsil
Summary: Here, we characterized the interaction between p53 and FOXO4 using NMR, chemical cross-linking, and analytical ultracentrifugation. Our findings highlight the importance of this interaction for the stability of the p53:FOXO4 complex and shed light on the intertwined functions of p53 and FOXO4 in cellular homeostasis, longevity, and stress response.
Review
Biochemistry & Molecular Biology
Veronika Obsilova, Tomas Obsil
Summary: Signal transduction cascades efficiently transmit chemical and/or physical signals from the extracellular environment to intracellular compartments, thereby eliciting an appropriate cellular response. 14-3-3 proteins, as a family of highly conserved scaffolding molecules, play a crucial role in modulating the function of other proteins primarily through phosphorylation-dependent mechanisms. They participate in key cellular processes such as cell-cycle control, apoptosis, signal transduction, energy metabolism, and protein trafficking. However, our understanding of the molecular mechanisms by which 14-3-3 proteins regulate their binding partners remains insufficient, despite intensive research into their protein-protein interactions. This review article aims to provide an overview of recent structural studies of 14-3-3 protein complexes in order to further explore the regulatory mechanisms of these proteins.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Dita Strachotova, Ales Holoubek, Katerina Wolfova, Barbora Brodska, Petr Herman
Summary: Specific C-terminal nucleophosmin (NPM) mutations are associated with acute myeloid leukaemia and cause mislocalization of NPMmut to the cytoplasm. This leads to mislocalization of NPM-interacting partners, including the tumor suppressor p53. We discovered the formation of a ternary complex consisting of NPMmut, p53, and Mdm2, with p53 acting as a bridging link between Mdm2 and NPMmut. Silencing of p53 prevented mislocalization of Mdm2 in the presence of NPMmut.
Article
Chemistry, Analytical
Dita Strachotova, Ales Holoubek, Barbora Brodska, Petr Herman
Summary: This study reports on the two-photon-induced photoconversion of EGFP, which can be permanently converted by intense IR irradiation to a form with a short fluorescence lifetime and spectrally conserved emission. The nonlinear dependence of the photoconversion efficiency on light intensity allows for accurate 3D localization of the converted volume within cellular structures, which is useful for kinetic FLIM applications.
METHODS AND APPLICATIONS IN FLUORESCENCE
(2023)
Article
Biochemistry & Molecular Biology
Olivia Petrvalska, Karolina Honzejkova, Nicola Koupilova, Petr Herman, Veronika Obsilova, Tomas Obsil
Summary: CaMKK1 and CaMKK2 are important protein kinases that play key roles in physiological and pathological processes. Complex formation affects their interaction with Ca2+/CaM and the structure of their domains, controlling their catalytic activity. The inhibitory effect of complex formation is more significant on CaMKK1 compared to CaMKK2, possibly due to the tighter and more rigid structure of the CaMKK1:14-3-3 gamma complex, which directly inhibits CaMKK1 activity.
Article
Biochemistry & Molecular Biology
Jakub Masaryk, Deepika Kale, Pavel Pohl, Francisco J. Ruiz-Castilla, Olga Zimmermannova, Veronika Obsilova, Jose Ramos, Hana Sychrova
Summary: Potassium is crucial for cellular processes, and its uptake and efflux through the plasma membrane need to be precisely regulated. The intracellular hydrophilic loop (IL2) of the Trk1 protein plays a key role in its targeting and activity regulation, and phosphorylation of specific residues within IL2 is important for these processes.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Meeting Abstract
Biochemistry & Molecular Biology
P. Pohl, T. Obsil, V. Obsilova
Meeting Abstract
Biochemistry & Molecular Biology
K. Kohoutova, V. Docekal, A. Tekel, M. Ausserlechner, J. Vesely, T. Obsil, V. Obsilova
Meeting Abstract
Biochemistry & Molecular Biology
R. Mandal, K. Kohoutova, O. Petrvalska, M. Horvath, P. Srb, V. Veverka, V. Obsilova, T. Obsil
Meeting Abstract
Biochemistry & Molecular Biology
K. Honzejkova, V. Obsilova, T. Obsil