Article
Biochemistry & Molecular Biology
Markus Rose, Martin Kurylowicz, Mohammad Mahmood, Sheldon Winkel, Jose M. Moran-Mirabal, Cecile Fradin
Summary: This study focuses on the interaction between two core members of the Bcl-2 family, Bax and tBid, revealing their different conformations on the membrane and their increased affinity when transitioning from loosely membrane-associated to transmembrane forms. The researchers used single particle imaging and cross-correlation analysis to infer protein conformation and detect transient interactions in a mitochondria-like planar supported lipid bilayer. This leads to an updated molecular model for the activation of Bax by tBid.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Tracy M. Josephs, Matthew J. Belousoff, Yi-Lynn Liang, Sarah J. Piper, Jianjun Cao, Daniel J. Garama, Katie Leach, Karen J. Gregory, Arthur Christopoulos, Debbie L. Hay, Radostin Danev, Denise Wootten, Patrick M. Sexton
Summary: This study provides insights into the mechanisms of class B1 GPCR activation by analyzing the structures and protein conformational dynamics of GPCRs.
Article
Chemistry, Multidisciplinary
Rama K. Koppisetti, Yan G. Fulcher, Steven R. Van Doren
Summary: The fusion peptide of SARS-CoV-2 plays a crucial role in the fusion of viral and cell membranes, with its structure changes affecting the fusion process between the virus and the cell.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Hui Lin, Peng Xiao, Rui-Qian Bu, Shengchao Guo, Zhao Yang, Daopeng Yuan, Zhong-Liang Zhu, Chuan-Xin Zhang, Qing-Tao He, Chao Zhang, Yu-Qi Ping, Ru-Jia Zhao, Chuan-Shun Ma, Chang-Hao Liu, Xiao-Ning Zhang, Dan Jiang, Shaohui Huang, Yue-Tong Xi, Dao-Lai Zhang, Chen-Yang Xue, Bai-Sheng Yang, Jian-Yuan Li, Hao-Cheng Lin, Xu-Hui Zeng, Han Zhao, Wen-Ming Xu, Fan Yi, Zhongmin Liu, Jin-Peng Sun, Xiao Yu
Summary: In this study, the cryo-EM structure of apo-ADGRG2 in complex with a G(s) trimer was solved, providing insights into the activation and ligand-binding of ADGRG2. The identification of steroid hormones, such as DHEA, as potential ligands of ADGRG2 was also reported.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Samantha Corra, Vanessa Checchetto, Michele Brischigliaro, Chiara Rampazzo, Emanuela Bottani, Cristina Gagliani, Katia Cortese, Cristiano De Pitta, Marco Roverso, Diego De Stefani, Sara Bogialli, Massimo Zeviani, Carlo Viscomi, Ildiko Szabo, Rodolfo Costa
Summary: Mutations in MPV17 contribute to mitochondrial DNA depletion syndromes, and this study shows that dMpv17 plays a role in mtDNA maintenance and energy homeostasis in Drosophila melanogaster.
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.
Review
Cell Biology
Chuankai Zhou
Summary: A major recent advance in cell biology is the understanding of the mechanisms and dynamics of biogenesis of membrane-less condensates. These condensates interact with membrane-bound organelles and are regulated by cellular signaling, metabolic states, and proteostasis network.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Chan Seok Lim, Yoon Ha Jang, Ga Young Lee, Gu Min Han, Hye Jin Jeong, Ji Won Kim, Jie-Oh Lee
Summary: Studies have shown that Toll-like Receptor 3 (TLR3) depends on the length of its ligands for triggering a robust immune response. In this study, the cryo-electron microscopy structure of TLR3 bound to a synthetic RNA ligand of average length 400 base pairs was determined. The structure revealed that TLR3 units form a highly organized and cooperative cluster along the double-stranded RNA helix, suggesting that ligand-induced clustering of TLR3 triggers the assembly of signaling adaptors and initiates a strong innate immune response.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Sabrina Pospich, Florian Kuellmer, Veselin Nasufovic, Johanna Funk, Alexander Belyy, Peter Bieling, Hans-Dieter Arndt, Stefan Raunser
Summary: This study presents the structures of a cell-permeable optojasp bound to actin filaments and highlights the effects of photoswitching a functionalized azobenzene for the first time. Analyzing the binding site and conformational changes within F-actin dependent on the optojasp isomeric state refines the determinants for designing functional F-actin photoswitches.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Jian Liu, Carrie Hiser, Fei Li, Robert Hall, R. Michael Garavito, Shelagh Ferguson-Miller
Summary: This article reports the structures of Rhodobacter sphaeroides TSPO and reveals that its structure is altered upon heme binding, providing potential clues about the structural basis of TSPO's role in heme delivery from mitochondria to the cytoplasm.
Article
Chemistry, Physical
Fabronia Murad, Ana J. Garcia-Saez
Summary: The Bcl-2 family proteins play crucial roles in regulating apoptosis by forming a complex network of interactions and regulating intracellular localization dynamics. Bax and tBid can shuttle between the cytosol and mitochondria independently, while Bcl-xL stabilizes tBid at mitochondria and promotes Bax retrotranslocation to the cytosol. Phosphorylation of Bcl-xL appears to regulate its function via multiple mechanisms in apoptosis regulation.
FARADAY DISCUSSIONS
(2021)
Article
Engineering, Chemical
Yang Liu, Guiliang Li, Qiu Han, Haibo Lin, Gang Deng, Qiang Li, Fu Liu
Summary: Protein-bound uremic toxins (PBUTs) have a significant impact on organ dysfunction, morbidity, and mortality in chronic kidney disease (CKD) patients. Traditional hemodialysis and hemoperfusion processes are ineffective in removing PBUTs due to their strong affinity with albumins. A novel adsorptive membrane incorporating amine/polyphenol/bimetal ions complexation was developed, which showed high affinity with uremic toxins and the ability to effectively remove them through continuous dialysis. The membrane also demonstrated excellent hemocompatibility and minimized immune responses.
JOURNAL OF MEMBRANE SCIENCE
(2023)
Review
Biochemistry & Molecular Biology
Priyanka Madhu, Samrat Mukhopadhyay
Summary: Soluble oligomers of Aβ play critical roles in Alzheimer's disease by causing synaptic dysfunction and memory impairments. These heterogeneous species have diverse characteristics that influence their biological effects in AD brains.
JOURNAL OF CELLULAR BIOCHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Dominic Gilzer, Madeleine Schreiner, Hartmut H. Niemann
Summary: This study reveals the binding mechanism between substrates and their chaperone and the cytosolic domain in virulent bacterial type III secretion systems. The interaction between the substrate and chaperone occurs at two distinct binding sites, and is essential for the formation of a functional secretion system.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Physical
Abigail Barclay, Birthe B. Kragelund, Lise Arleth, Martin Cramer Pedersen
Summary: Recent advances in protein expression protocols have allowed for the investigation of structurally complex and disordered biomolecules using small-angle scattering experiments. A modeling scheme has been developed that combines classical form factor based modeling with spherical harmonics-based formulation to accurately calculate scattering profiles from these complex samples. The scheme can account for flexible domains and other structurally elaborate components, and we demonstrate its utility through a case study on a growth hormone receptor membrane protein. We also explore how the scattering profiles vary under different contrasts and discuss the implications for data modeling.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Article
Biochemical Research Methods
K. Ashley Hickman, Santosh Hariharan, Jason De Melo, Jarkko Ylanko, Lindsay C. Lustig, Linda Z. Penn, David W. Andrews
Article
Cell Biology
Wiebke Schormann, Santosh Hariharan, David W. Andrews
JOURNAL OF CELL BIOLOGY
(2020)
Article
Oncology
Joseph Longo, Petr Smirnov, Zhihua Li, Emily Branchard, Jenna E. van Leeuwen, Jonathan D. Licht, Benjamin Haibe-Kains, David W. Andrews, Jonathan J. Keats, Trevor J. Pugh, Suzanne Trudel, Linda Z. Penn
Summary: This study revealed that t(4;14)-positive multiple myeloma cells depend on the mevalonate (MVA) pathway for survival and are sensitive to statin treatment. Statins induce apoptosis in t(4;14)-positive cells and synergize with bortezomib to enhance anti-tumor activity.
Article
Multidisciplinary Sciences
Albane Thery, Lucas Le Nagard, Jean-Christophe Ono-dit-Biot, Cecile Fradin, Kari Dalnoki-Veress, Eric Lauga
SCIENTIFIC REPORTS
(2020)
Article
Biochemical Research Methods
Philipp Mergenthaler, Santosh Hariharan, James M. Pemberton, Corey Lourenco, Linda Z. Penn, David W. Andrews
Summary: The study introduces a comprehensive shallow-learning framework for automated quantitative phenotyping of three-dimensional image data, using unsupervised data-driven voxel-based feature learning. By implementing image analysis algorithms called Phindr3D, rapid application of data-driven voxel-based feature learning into 3D high content analysis (HCA) operations is achieved, demonstrating potential in analyzing complex 3D images of neurons and organoids. This novel approach allows for facile discovery and interpretation of meaningful patterns in high dimensional feature space without the need for complex image processing or prior assumptions.
PLOS COMPUTATIONAL BIOLOGY
(2021)
Article
Chemistry, Medicinal
Justin P. Pogmore, David Uehling, David W. Andrews
Summary: Although Venetoclax has achieved success in treating lymphoid malignancies by targeting the antiapoptotic protein BCL-2, there is still a need for improved targeting of pro-apoptotic proteins such as BAX, BAK, and BOK. Recent research indicates that small molecule tool compounds can positively or negatively regulate these proteins, affecting the regulation of apoptosis.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Aleena L. Patel, Lili Zhang, Shannon E. Keenan, Christine A. Rushlow, Cecile Fradin, Stanislav Y. Shvartsman
Summary: This study investigates the dynamics of transcriptional repression by Capicua (Cic) in early Drosophila embryos, revealing the speed limit and mechanism of rapid gene repression by Cic. It sets quantitative constraints on potential mechanisms for gene regulation by Cic, providing insights for future studies in gene regulation mechanisms.
Article
Engineering, Electrical & Electronic
Nehad Hirmiz, Anthony Tsikouras, Elizabeth J. Osterlund, Morgan Richards, David W. Andrews, Qiyin Fang
Summary: A high-speed multiplexed confocal microscope system has been developed for measuring protein-protein interactions and generating binding curves in live cells. The results demonstrate the system's effectiveness in screening for protein-protein interactions in drug discovery applications.
IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS
(2021)
Article
Biochemistry & Molecular Biology
Markus Rose, Martin Kurylowicz, Mohammad Mahmood, Sheldon Winkel, Jose M. Moran-Mirabal, Cecile Fradin
Summary: This study focuses on the interaction between two core members of the Bcl-2 family, Bax and tBid, revealing their different conformations on the membrane and their increased affinity when transitioning from loosely membrane-associated to transmembrane forms. The researchers used single particle imaging and cross-correlation analysis to infer protein conformation and detect transient interactions in a mitochondria-like planar supported lipid bilayer. This leads to an updated molecular model for the activation of Bax by tBid.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Elizabeth J. Osterlund, Nehad Hirmiz, James M. Pemberton, Adrien Nougarede, Qian Liu, Brian Leber, Qiyin Fang, David W. Andrews
Summary: Cytoplasmic and membrane-bound BCL-2 family proteins regulate apoptosis, and the effects of inhibitors in live cells are difficult to measure. This study compared different BH3 mimetic drugs using fluorescence microscopy and evaluated their effects on protein binding in cells.
Article
Multidisciplinary Sciences
Jenna E. van Leeuwen, Wail Ba-Alawi, Emily Branchard, Jennifer Cruickshank, Wiebke Schormann, Joseph Longo, Jennifer Silvester, Peter L. Gross, David W. Andrews, David W. Cescon, Benjamin Haibe-Kains, Linda Z. Penn, Deena M. A. Gendoo
Summary: The study shows that dipyridamole can enhance statin-induced cancer cell death. To identify similar compounds, an integrative pharmacogenomics pipeline is developed based on drug structure, cell sensitivity, and molecular perturbation. The effectiveness of nelfinavir and honokiol is validated, and low expression of E-cadherin is found to be associated with statin-compound synergy.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Elizabeth J. Osterlund, Nehad Hirmiz, Dang Nguyen, James M. Pemberton, Qiyin Fang, David W. Andrews
Summary: The ER-resident protein BIK interacts directly with antiapoptotic proteins localized to mitochondria, promoting mitochondrial outer membrane permeabilization and initiating apoptosis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Biology
James M. Pemberton, Dang Nguyen, Elizabeth J. Osterlund, Wiebke Schormann, Justin P. Pogmore, Nehad Hirmiz, Brian Leber, David W. Andrews
Summary: The anti-apoptotic protein PUMA resists displacement by BH3 mimetics through its binding with both the BH3 motif and a novel binding site within the carboxyl-terminal sequence (CTS). Understanding this resistance mechanism will aid in the design of more effective anti-apoptotic protein inhibitors.
Article
Physics, Fluids & Plasmas
Liu Yu, Lucas Le Nagard, Solomon Barkley, Lauren Smith, Cecile Fradin
Summary: The helical-shaped magnetotactic bacteria provide a unique opportunity for studying the translational and rotational friction coefficients of micron-sized chiral particles. The results suggest that the rotational motion of the cell body could significantly contribute to cellular propulsion.
Review
Biochemistry & Molecular Biology
James M. Pemberton, Justin P. Pogmore, David W. Andrews
Summary: Axonal degeneration and neuronal cell death are regulated by BCL-2 family proteins, with potential influences from other cell death pathways. Deciphering the subsets of proteins required and separately regulating these outcomes is essential for future research and pharmacological interventions.
CELL DEATH AND DIFFERENTIATION
(2021)