Article
Multidisciplinary Sciences
Lena Voith von Voithenberg, Anders Barth, Vanessa Trauschke, Benjamin Demarco, Swati Tyagi, Christine Koehler, Edward A. Lemke, Don C. Lamb
Summary: The correct folding of proteins inside the cell is crucial for cellular function. Heat-shock proteins 70 (Hsp70s) play a key role in this process by undergoing coordinated structural rearrangements to aid in protein folding and transport. Using three-color single-molecule FRET, researchers identified coordinated structural changes during the functional cycle of DnaK, Ssc1, and BiP chaperones, revealing the flexibility and variability in their recognition mechanism for nucleotides. The study provides a detailed characterization of the conformational space of proteins at a higher resolution than traditional single-distance approaches in single-molecule FRET.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Correction
Chemistry, Multidisciplinary
Ming-Jie Han, Qing-tao He, Mengyi Yang, Chao Chen, Yirong Yao, Xiaohong Liu, Yuchuan Wang, Zhong-liang Zhu, Kong-kai Zhu, Changxiu Qu, Fan Yang, Cheng Hu, Xuzhen Guo, Dawei Zhang, Chunlai Chen, Jin-peng Sun, Jiangyun Wang
Summary: The study corrected and analyzed beta-arrestin-1 at the single-molecule level using genetic code expansion and a Se-click reaction, providing important insights into the function and structure of this protein for further research.
Review
Biochemistry & Molecular Biology
David P. Millar
Summary: This article describes the smFRET methods used to probe the conformational dynamics of DNA polymerases, with a focus on E. coli DNA polymerase I. The studies reviewed reveal the conformational dynamics underlying the nucleotide selection, proofreading, and 5' nuclease activities of Pol I, which are likely employed across the DNA polymerase family. smFRET methods have also been used to examine other aspects of DNA polymerase activity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Physical
Hector Vazquez
Summary: This method uses density functional theory to calculate the tunneling conductance of single molecule junctions, simplifying the model and reducing computational costs significantly, while also quantifying the relationship between molecular structure and conductance.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2022)
Article
Biochemistry & Molecular Biology
Wesley B. Asher, Daniel S. Terry, G. Glenn A. Gregorio, Alem W. Kahsai, Alessandro Borgia, Bing Xie, Arnab Modak, Ying Zhu, Wonjo Jang, Alekhya Govindaraju, Li-Yin Huang, Asuka Inoue, Nevin A. Lambert, Vsevolod V. Gurevich, Lei Shi, Robert J. Lefkowitz, Scott C. Blanchard, Jonathan A. Javitch
Summary: Beta-arrestins are strongly autoinhibited in their basal state but can be activated by phosphorylated receptors and receptor agonism, releasing the beta-arrestin tail and allowing it to assume different conformations. The rate and efficiency of beta-arrestin activation depend on the phosphorylation pattern of the receptor and agonist-promoted receptor activation.
Article
Chemistry, Multidisciplinary
Yuna Bae, Min Young Ha, Ki-Taek Bang, Sanghee Yang, Sung Yun Kang, Joodeok Kim, Jongbaek Sung, Sungsu Kang, Dohun Kang, Won Bo Lee, Tae-Lim Choi, Jungwon Park
Summary: This paper utilizes liquid-phase transmission electron microscopy to track the real-time dynamics of single-chain polymers, revealing the conformational characteristics of these polymers and their dependence on intrachain interactions and environmental factors.
ADVANCED MATERIALS
(2022)
Article
Chemistry, Applied
Wenyang Zhao, Zeyang Ding, Bao Li, Chunrong Chen, Houyu Zhang, Shimei Jiang
Summary: In this study, a series of salicylaldehyde Schiff base derivatives with different alkoxy chain lengths (NPA-n, n = 1, 4, 8, 12) were synthesized, which exhibited tunable emissions in both solution and solid states. The research provides a new strategy for constructing multi-color fluorophores for various applications.
Article
Multidisciplinary Sciences
Yanyan Xue, Jun Li, Dian Chen, Xizhu Zhao, Liang Hong, Yu Liu
Summary: This study develops a method to monitor the conformational change of riboSAM during transcription, and observes five co-existing states in riboSAM. A bifurcated helix structure is identified in one of the states and is found to be responsible for translation inhibition. This strategy enables the precise mapping of RNA conformational landscape during transcription.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Nathan Ponzar, Nicola Pozzi
Summary: Disulfide bonds are essential for protein folding and stability, and dysregulation of this process can lead to various disorders. Thiol-isomerases (TIs) are a family of enzymes that oversee this process in human cells. However, our understanding of how TIs select and interact with their substrates, as well as their response to changes in redox environment, remains limited.
Article
Chemistry, Multidisciplinary
Hua Zhang, Wei Xu, Kai Song, Taige Lu, Guanxin Zhang, Yaping Zang, Wenjing Hong, Deqing Zhang
Summary: In this study, single-molecule conductance studies of TBT1-TBT6 with the scanning tunneling microscope break junction (STM-BJ) technique were reported. It was found that the molecular conductance of TBT1 with intramolecular O center dot center dot center dot S noncovalent interactions is significantly enhanced compared to their analogue TBT2. Additionally, the conductance of TBT3, TBT4, and TBT5 can be boosted by increasing the electric field applied to the molecular junctions. The results demonstrate the potential of molecules with intramolecular O center dot center dot center dot S noncovalent interactions for in situ control of the electrical properties of molecular-scale devices.
Review
Biochemistry & Molecular Biology
Inbal Riven, Hisham Mazal, Marija Iljina, Gilad Haran
Summary: Recent research has shown that tertiary-structure dynamics in certain proteins can occur on a very fast timescale. This review discusses the relationship between ultrafast domain motions and the function of ClpB, a protein involved in rescuing protein chains from aggregates. Single-molecule FRET spectroscopy was used to study the dynamics of essential structural elements in ClpB, revealing fast toggling of its middle domain and motion restrictions of the N-terminal domain. The dynamics of pore loops and their response to perturbations suggest a Brownian-ratchet mechanism for protein translocation.
Article
Biochemistry & Molecular Biology
Christin Fuks, Sebastian Falkner, Nadine Schwierz, Martin Hengesbach
Summary: Riboswitch RNAs regulate gene expression through conformational changes induced by environmental conditions and specific ligand binding, which is of great significance for understanding the mechanism of RNA regulation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Chemistry, Physical
Aljaz Godec, Dmitrii E. Makarov
Summary: In this paper, we discuss the practical challenges of using stochastic thermodynamics to determine the directionality of molecular machines from experimental single-molecule trajectories. Due to the limitations of spatiotemporal resolution in these experiments and the inability to detect both forward and backward transitions between the same states, distinguishing the forward and backward directions of ATP-consuming periodic molecular machines becomes a nontrivial task. By extending the commonly used Markov-state model to analyze single-molecule transition-path measurements, we show how irreversibility can be hidden in these measurements but can be revealed when non-Markov effects in low-dimensional single-molecule trajectories are considered.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Physical
Ikenna C. Okafor, Taekjip Ha
Summary: CRISPR Cas9 is an RNA-guided endonuclease that is a part of bacterial adaptive immune system. By developing a single molecule FRET assay, the study investigated the conformational changes of sgRNA and the binding of Cas9 to sgRNA, providing insights into the assembly dynamics of Cas9 RNA ribonucleoprotein complex. This research could contribute to the rational design of sgRNAs and improve the editing outcomes.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Physical
Nicole Stephanie Galenkamp, Giovanni Maglia
Summary: The study demonstrates the dynamic exchange between five structural intermediates during DHFR catalysis in E. coli through nanopore currents. An endosteric effect promotes substrate binding to the enzyme and the chemical step switches the enzyme from closed to occluded conformation, leading to the release of the reduced cofactor. Only a few reactive complexes lead to catalysis, and second-long catalytic pauses were observed. Multiple cofactor binding events are required to release the product and switch DHFR back to the reactive conformer.
Article
Chemistry, Physical
Sonja Schmid, Markus Goetz, Thorsten Hugel
Article
Chemistry, Physical
Sonja Schmid, Thorsten Hugel
JOURNAL OF CHEMICAL PHYSICS
(2018)
Article
Biochemistry & Molecular Biology
Markus Jahn, Katarzyna Tych, Hannah Girstmair, Maximilian Steinmassl, Thorsten Hugel, Johannes Buchner, Matthias Rief
Article
Chemistry, Physical
Bjorn Hellenkamp, Johann Thurn, Martina Stadlmeier, Thorsten Hugel
JOURNAL OF PHYSICAL CHEMISTRY B
(2018)
Article
Chemistry, Multidisciplinary
Sofia Brander, Thomas Jank, Thorsten Hugel
Article
Chemistry, Multidisciplinary
Adrianna Kolberg, Christiane Wenzel, Klara Hackenstrass, Richard Schwarzl, Christian Ruettiger, Thorsten Hugel, Markus Gallei, Roland R. Netz, Bizan N. Balzer
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2019)
Article
Biology
Sonja Schmid, Thorsten Hugel
Article
Engineering, Biomedical
Mathaeus Tschaikowsky, Tanja Neumann, Sofia Brander, Heiko Haschke, Bernd Rolauffs, Bizan N. Balzer, Thorsten Hugel
Summary: Understanding the function and dysfunction of hierarchically organized biomaterials or tissues requires studying different length scales. Atomic force microscopy (AFM) combined with fluorescence microscopy can provide detailed information from millimeter to nanometer scales. This approach is not only applicable to cartilage but also useful for characterizing native biological tissues from macro- to nanoscale.
ACTA BIOMATERIALIA
(2021)
Article
Chemistry, Multidisciplinary
Max Lallemang, Leixiao Yu, Wanhao Cai, Klaus Rischka, Andreas Hartwig, Rainer Haag, Thorsten Hugel, Bizan N. Balzer
Summary: This study investigates the strength and characteristics of multivalent interactions at the molecular level using AFM technology, and finds that under certain conditions, non-covalent bonds, such as coordination bonds, can exhibit higher multivalent bond strength, even surpassing strong covalent bonds. Additionally, covalent bonds enhance the density of the multifunctional polymer layer, particularly increasing the number of non-covalent bonds.
Article
Engineering, Biomedical
Mathaeus Tschaikowsky, Sofia Brander, Vanessa Barth, Ralf Thomann, Bernd Rolauffs, Bizan N. Balzer, Thorsten Hugel
Summary: This study reveals changes in the thickness and composition of collagen fibers at the onset of osteoarthritis. Fibrocartilage-like tissue rich in type I collagen is formed in intact cartilage during the early stages of the disease, while thick fibers are completely absent in advanced osteoarthritis. The findings provide insights into the understanding of other native biological tissues and the development of sustainable biomaterials.
ACTA BIOMATERIALIA
(2022)
Article
Chemistry, Multidisciplinary
Wanhao Cai, Miriam Jaeger, Jakob T. Bullerjahn, Thorsten Hugel, Steffen Wolf, Bizan N. Balzer
Summary: In this study, the rupture force and friction of the biotin-streptavidin complex under a externally applied force were investigated using AFM-based single molecule force spectroscopy and molecular dynamics simulations. Anisotropic friction, arising from an experimentally uncontrolled orientation parameter, was identified. The study suggests that anisotropic friction should be taken into account for a complete understanding of friction in biomolecular dynamics and anisotropic mechanical environments.
Article
Biophysics
Tanumoy Mondol, Laura-Marie Silbermann, Julia Schimpf, Leonie Vollmar, Bianca Hermann, Katarzyna (Kasia) Tych, Thorsten Hugel
Summary: This study reveals that Aha1 regulates various functions of Hsp90, including conformation, kinetics, ATPase activity, and stability, through different binding stoichiometries. This finding is of great significance for further understanding of Hsp90 and its regulatory mechanisms in cellular processes.
BIOPHYSICAL JOURNAL
(2023)
Article
Multidisciplinary Sciences
Chenyang Lan, Juhyeong Kim, Svenja Ulferts, Fernando Aprile-Garcia, Sophie Weyrauch, Abhinaya Anandamurugan, Robert Grosse, Ritwick Sawarkar, Aleks Reinhardt, Thorsten Hugel
Summary: This study quantifies the formation of NELF protein clusters in stressed cells and finds a broad distribution of pre-condensate cluster sizes. The formation of NELF protein clusters can be explained as non-classical nucleation with a surprisingly flat free-energy landscape.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Wanhao Cai, Jakob T. Bullerjahn, Max Lallemang, Klaus Kroy, Bizan N. Balzer, Thorsten Hugel
Summary: In this study, stereographic force spectroscopy was established to investigate the single-bond strength at different pulling angles. The results showed that the bond strength increased with increasing pulling angle, indicating a mechanical anisotropy of the chemical bond.
Article
Chemistry, Multidisciplinary
Steffen Wolf, Benedikt Sohmen, Bjorn Hellenkamp, Johann Thurn, Gerhard Stock, Thorsten Hugel
Summary: The study investigates how ATP hydrolysis causes structural changes in proteins and the hierarchical dynamics process using Hsp90 as a model system.
The process involves timescales ranging from nanoseconds to milliseconds and length scales from angstroms to several nanometers, with conformational changes and structural information transfer leading to structural asymmetry in proteins.
The findings suggest that similar mechanisms may be fundamental for information transfer induced by ATP hydrolysis in many other proteins.