Article
Biology
Holly C. Ford, William J. Allen, Goncalo C. Pereira, Xia Liu, Mark Simon Dillingham, Ian Collinson
Summary: This article describes the import process of mitochondrial proteins and the research progress in understanding its mechanisms. Using a newly developed assay based on split NanoLuc luciferase, researchers found that the size and net charge of pre-sequences influence the import process, which is driven by the transmembrane potential and ATP hydrolysis. The study also revealed the functional differences between the two membranes involved in the import process.
Article
Chemistry, Physical
Samuel D. Winter, Hannah B. L. Jones, Dora M. Rasadean, Rory M. Crean, Michael J. Danson, G. Dan Panto, Gergely Katona, Erica Prentice, Vickery L. Arcus, Marc W. van der Kamp, Christopher R. Pudney
Summary: This study investigates how individual substrate interactions affect the temperature dependence of enzyme activity and the network of motions throughout the protein, revealing how subtle changes in substrate binding can affect global changes in motion and flexibility extending throughout the protein.
Article
Biochemistry & Molecular Biology
Xueyin Zhou, Yuqi Yang, Guopeng Wang, Shanshan Wang, Dongjie Sun, Xiaomin Ou, Yuke Lian, Long Li
Summary: This study reports the mechanism of mitochondrial protein import via the pre-sequence pathway through the TOM-TIM23 supercomplex. Cryo-EM and structural analyses reveal that polypeptide substrates pass through the TOM complex and enter the TIM23 complex via a negatively charged entrance and a central hydrophobic region.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jose A. Villegas, Tasneem M. Vaid, Michael E. Johnson, Terry W. Moore
Summary: A major challenge in computational modeling of macromolecules is the vast conformational space due to atomic degrees of freedom. Recent interest in predictive models of complexes mediated by PROTACs led to the application of advanced computational techniques. However, repurposing existing tools for protein-protein docking and linker conformer generation results in incompatible structures. In this study, a cyclic coordinate descent algorithm was used to position PROTACs into complex-bound configurations, allowing for a restricted search in protein-protein conformations that can be bridged by a PROTAC molecule with a given linker composition.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Oncology
Mehdi Sharifi Tabar, Habib Francis, Dannel Yeo, Charles G. Bailey, John E. J. Rasko
Summary: Normal protein-protein interactions (normPPIs) play a crucial role in regulating physiological processes, but in cancer, this organized network is disrupted, leading to oncogenic protein-protein interactions (oncoPPIs). Recent advancements in mass spectrometry (MS), structural biology, and drug discovery have allowed scientists to identify and characterize oncoPPIs. However, the construction of a reference oncoPPI map for different types of cancers is still lacking due to technical challenges. Therefore, there is an urgent need to develop experimental workflows to overcome these challenges and create comprehensive reference maps.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Review
Physiology
Marcel G. Genge, Dejana Mokranjac
Summary: The majority of mitochondrial proteins are synthesized in the cytosol and contain specific mitochondrial targeting signals. These signals, such as presequences, help guide the proteins to the mitochondrial matrix with the assistance of TOM and TIM23 complexes in the outer and inner membranes. The TOM and TIM23 complexes interact in the intermembrane space, facilitating the transfer of presequences and precursor proteins from the outer to the inner mitochondrial membrane.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Liangliang Shen, Kailu Tang, Wenda Wang, Chen Wang, Hangjun Wu, Zhiyuan Mao, Shaoya An, Shenghai Chang, Tingyun Kuang, Jian-Ren Shen, Guangye Han, Xing Zhang
Summary: The study presents the cryo-electron microscopy structures of a PSI-NDH supercomplex from barley, revealing the composition and interactions of its internal subunits. It provides a structural basis for further investigations on the functions and regulation of PSI-NDH-dependent cyclic electron transport (CET).
Article
Chemistry, Multidisciplinary
Wenzhe Liu, Jie Li, Yongping Xu, Dongbao Yin, Xin Zhu, Huanyan Fu, Xiaodong Su, Xuefeng Guo
Summary: The study utilized high-gain silicon nanowire field-effect transistors for label-free detection of DNA-protein interaction, visualizing the binding process with single-base resolution. The swinging of hydrogen bonds between amino acid residues and DNA bases induced dynamic collective motion between DNA-binding protein and DNA.
Article
Multidisciplinary Sciences
Qiang Wang, Zeyuan Guan, Liangbo Qi, Jinjin Zhuang, Chen Wang, Sixing Hong, Ling Yan, Yan Wu, Xiaoqian Cao, Jianbo Cao, Junjie Yan, Tingting Zou, Zhu Liu, Delin Zhang, Chuangye Yan, Ping Yin
Summary: Sam37 stabilizes mature Tom40 mainly through electrostatic interactions, facilitating subsequent TOM assembly. These results support the b barrel switching model and offer structural insights into the assembly and release of b barrel complexes.
Article
Multidisciplinary Sciences
Alexander Muhleip, Rasmus Kock Flygaard, Rozbeh Baradaran, Outi Haapanen, Thomas Gruhl, Victor Tobiasson, Amandine Marechal, Vivek Sharma, Alexey Amunts
Summary: In this study, it was revealed that a supercomplex containing all four respiratory chain components contributes to membrane curvature induction in ciliates. Cryo-electron microscopy and cryo-tomography techniques were used to determine the structure of the supercomplex, which is composed of 150 different proteins and 311 bound lipids. Molecular dynamics simulations demonstrated that the divergent supercomplex actively contributes to membrane curvature induction and tubulation of cristae. These findings highlight the evolutionary significance of protein subunits of respiratory complexes in shaping the bioenergetic membrane for functional specialization.
Article
Multidisciplinary Sciences
Dvir Harris, Hila Toporik, Gabriela S. Schlau-Cohen, Yuval Mazor
Summary: The study reveals that photosynthetic supercomplexes exhibit a wide range of conformations but maintain their efficiency due to specific chlorophylls. These protein complexes are essential for converting solar energy with high efficiency. Despite variability in protein organization, the energy transfer efficiency remains consistent. This finding contributes to a better understanding of the mechanism of photosynthesis.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Zeyu Jin, Li Wan, Yuqi Zhang, Xuecheng Li, Yong Cao, Haobin Liu, Shengyao Fan, Du Cao, Zhengmao Wang, Xiaobo Li, Junmin Pan, Meng-Qiu Dong, Jianping Wu, Zhen Yan
Summary: This study reports the structure of the TOC-TIC supercomplex from Chlamydomonas, providing insights into its composition, assembly, and preprotein translocation mechanism. The findings lay a foundation for interpreting the evolutionary conservation and diversity of this fundamental translocon machinery.
Article
Cell Biology
Isabel Beets, Sven Zels, Elke Vandewyer, Jonas Demeulemeester, Jelle Caers, Esra Baytemur, Amy Courtney, Luca Golinelli, Ilayda Hasakiogullari, William R. Schafer, Petra E. Vertes, Olivier Mirabeau, Liliane Schoofs
Summary: Neuropeptides and peptide hormones are widespread signaling molecules that play important roles in brain functions. In this study, the researchers created a peptide-GPCR interaction map in Caenorhabditis elegans, uncovering a broad signaling network with specific and complex interactions. These findings provide insights into the functions and evolution of peptides.
Article
Endocrinology & Metabolism
Qiongya Zhao, Ting Luo, Feng Gao, Yinxu Fu, Bin Li, Xiaoli Shao, Haifeng Chen, Zhuohua Zhou, Sihan Guo, Lijun Shen, Liqin Jin, Dong Cen, Huaibin Zhou, Jianxin Lyu, Hezhi Fang
Summary: GRP75 plays a key role in regulating mitochondrial function and insulin sensitivity. The study found that GRP75 expression was downregulated in mice fed a high-fat diet, and inducing GRP75 could prevent obesity and insulin resistance. Mechanistically, GRP75 regulates insulin sensitivity through its modulation of mitochondrial supercomplex turnover.
Article
Engineering, Biomedical
Talha Burak Alakus, Ibrahim Turkoglu
Summary: Protein-protein interactions play crucial roles in cellular functions and target organism functions, experimental methods are used to determine these interactions, however computational approaches are more advantageous in addressing high false positive interactions.
BIOMEDICAL SIGNAL PROCESSING AND CONTROL
(2021)
Article
Multidisciplinary Sciences
Ying Zhang, Evelina De Laurentiis, Katherine E. Bohnsack, Mascha Wahlig, Namit Ranjan, Simon Gruseck, Philipp Hackert, Tina Wolfle, Marina Rodnina, Blanche Schwappach, Sabine Rospert
Summary: The GET pathway aids in delivering tail-anchored proteins to the ER, with Get4/5 components probing near the ribosomal exit tunnel and recruiting Sgt2 upon emergence of client proteins to initiate the targeting phase of the pathway.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Akos Farkas, Henning Urlaub, Katherine E. Bohnsack, Blanche Schwappach
Summary: The study reveals the important role of the guided entry of tail-anchored proteins (GET) pathway in lipotoxicity and uncovers the hairpin membrane protein Erg1 as a non-canonical GET pathway client. The GET pathway is particularly important for the acute upregulation of Erg1 under low sterol conditions, and several other proteins anchored to the endoplasmic reticulum via a hairpin are also identified as potential GET clients.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Biochemical Research Methods
Mark Bates, Jan Keller-Findeisen, Adrian Przybylski, Andreas Hueper, Till Stephan, Peter Ilgen, Angel R. Cereceda Delgado, Elisa D'Este, Alexander Egner, Stefan Jakobs, Steffen J. Sahl, Stefan W. Hell
Summary: The dynamic model of the 4Pi point spread function allows for high three-dimensional resolution in localization microscopy. 4Pi-STORM imaging reveals nanoscale details of protein and nucleic acid organization in neurons and mitochondria. Despite challenges in instrumentation and data analysis, the development of a 4Pi-STORM microscope with dynamic PSF modeling and simpler optical design offers optimal resolution and accuracy for molecular organization studies.
Article
Biochemistry & Molecular Biology
Sung-Hui Yi, Valentyn Petrychenko, Jan Erik Schliep, Akanksha Goyal, Andreas Linden, Ashwin Chari, Henning Urlaub, Holger Stark, Marina Rodnina, Sarah Adio, Niels Fischer
Summary: This study reveals key intermediates during translation initiation in human cells using cryo-EM structures and kinetic methods. The results show the formation of two distinct ribosome populations, representing stages before and after codon recognition in the presence of specific initiation factors. The study also highlights differences in the start codon selection mechanism between humans and yeast.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Eden Yifrach, Markus Rudowitz, Luis Daniel Cruz-Zaragoza, Asa Tirosh, Zohar Gazi, Yoav Peleg, Markus Kunze, Miriam Eisenstein, Wolfgang Schliebs, Maya Schuldiner, Ralf Erdmann, Einat Zalckvar
Summary: This study reveals that the targeting specificity of peroxisomal proteins in yeast is mainly determined by the hydrophobic nature of the amino acid preceding the PTS1 signal. Structural modeling shows differences in surface hydrophobicity of the PTS1-binding cavities of the two factors. This work elucidates the mechanism by which targeting specificity is achieved, enabling dynamic rewiring of the peroxisomal proteome in response to changing metabolic needs.
BIOLOGICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Lynn M. Ostersehlt, Daniel C. Jans, Anna Wittek, Jan Keller-Findeisen, Kaushik Inamdar, Steffen J. Sahl, Stefan W. Hell, Stefan Jakobs
Summary: The combination of MINFLUX nanoscopy with DNA-PAINT labeling enables multi-color imaging of multiple molecular targets, leading to improved nanoscopy in fixed cells and increased multiplexing in MINFLUX imaging, as demonstrated by three-color imaging of mitochondria in mammalian cells.
Article
Multidisciplinary Sciences
Franziska Nadler, Elena Lavdovskaia, Angelique Krempler, Luis Daniel Cruz-Zaragoza, Sven Dennerlein, Ricarda Richter-Dennerlein
Summary: The study investigates the translation termination mechanism for the non-conventional mtDNA-encoded COX1 and ND6, and identifies mtRF1 as the release factor for COX1 and mtRF1a for other mitochondrial translation events including ND6.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Tobias Bock-Bierbaum, Kathrin Funck, Florian Wollweber, Elisa Lisicki, Karina von der Malsburg, Alexander von der Malsburg, Janina Laborenz, Jeffrey K. Noel, Manuel Hessenberger, Sibylle Jungbluth, Carola Bernert, Severine Kunz, Dietmar Riedel, Hauke Lilie, Stefan Jakobs, Martin van der Laan, Oliver Daumke
Summary: Mitochondrial cristae membranes are where oxidative phosphorylation occurs in cells, and cristae junctions serve as selective entry gates into the cristae space. The Mic60-Mic19 subcomplex acts as a molecular strut, controlling the architecture and function of cristae junctions.
Article
Multidisciplinary Sciences
Tianyan Liu, Till Stephan, Peng Chen, Jan Keller-Findeisen, Jingting Chen, Dietmar Riedel, Zhongtian Yang, Stefan Jakobs, Zhixing Chen
Summary: This study reports a mitochondrial inner membrane fluorescent marker, PK Mito Orange (PKMO), which features reduced phototoxicity and high stability, enabling super-resolution recordings of mitochondrial inner membrane dynamics. The PKMO dye is optically orthogonal with green and far-red markers, allowing multiplexed recordings. By using multi-color STED microscopy, interactions between mitochondria and other cellular components can be captured at sub-100 nm resolution.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Naintara Jain, Ridhima Gomkale, Olaf Bernhard, Peter Rehling, Luis Daniel Cruz-Zaragoza
Summary: Mitochondria play a crucial role in cellular energy production and metabolism, and errors in mitochondrial protein import can lead to metabolic disorders. This study establishes a fluorescence-based import assay to analyze protein import into mitochondria, offering the advantage of quantifying import with high sensitivity. The assay can be adapted to a screening-compatible format and used to monitor the assembly of the F1F0 ATP synthase in purified mitochondria.
Article
Multidisciplinary Sciences
Olexandr Dybkov, Marco Preussner, Leyla El Ayoubi, Vivi-Yun Feng, Caroline Harnisch, Kilian Merz, Paula Leupold, Peter Yudichev, Dmitry E. Agafonov, Cindy L. Will, Cyrille Girard, Christian Dienemann, Henning Urlaub, Berthold Kastner, Florian Heyd, Reinhard Luehrmann
Summary: Alternative precursor messenger RNA splicing expands the proteome of higher eukaryotes, and changes in 3'ss usage contribute to human disease. Through knockdowns and RNA sequencing, we found that proteins recruited to human C* spliceosomes regulate alternative splicing, including the selection of NAGNAG 3'ss. Cryo-electron microscopy and protein cross-linking provide insights into the molecular architecture of these proteins and how they influence 3'ss usage. Our studies reveal widespread regulation of alternative 3'ss usage and the mechanisms by which C* proteins influence NAGNAG 3'ss choices.
Article
Biochemistry & Molecular Biology
Ying Chen, Goran Kokic, Christian Dienemann, Olexandr Dybkov, Henning Urlaub, Patrick Cramer
Summary: Through cryo-EM structures, it was discovered that Elongin binds to a specific region on Pol II and regulates the conformational mobility of the polymerase, thus playing a role in transcription.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Correction
Biology
Vahid Ebrahimi, Till Stephan, Jiah Kim, Pablo Carravilla, Christian Eggeling, Stefan Jakobs, Kyu Young Han
COMMUNICATIONS BIOLOGY
(2023)
Article
Biology
Vahid Ebrahimi, Till Stephan, Jiah Kim, Pablo Carravilla, Christian Eggeling, Stefan Jakobs, Kyu Young Han
Summary: This study demonstrates that restoring STED microscopy images using deep learning can reduce the effects of photobleaching and photodamage by decreasing the pixel dwell time. Our method effectively and reliably restores noisy 2D and 3D STED images, enabling long-term observation of mitochondrial dynamics.
COMMUNICATIONS BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Dojin Kim, Stefan Stoldt, Michael Weber, Stefan Jakobs, Vladimir N. N. Belov, Stefan W. W. Hell
Summary: Disulfonated rhodamines, commonly used in life science and optical microscopy, were previously thought to be impermeable to living cells. This assumption was challenged by using five popular rhodamines combined with a HaloTag (TM) amine (O-2) ligand (x) to successfully label living cells. Three compounds with two negative charges, Rho590-x, Rho565-x, and Rho530-x, showed specific and bright staining in living cells and performed well in STED microscopy. Other probes with one negative charge, prepared by native chemical ligation and esterification, exhibited specific staining and red shifts in absorption and emission bands.