Article
Chemistry, Multidisciplinary
Albert A. Smith, Emelyne M. Pacull, Sabrina Stecher, Peter W. Hildebrand, Alexander Vogel, Daniel Huster
Summary: G protein-coupled receptors initiate signal transduction by binding with ligands. In this study, we focus on the growth hormone secretagogue receptor (GHSR), which binds with the 28 residue peptide ghrelin. We compared the dynamics of apo and ghrelin-bound GHSR using long molecular dynamics simulation trajectories and identified differences in dynamics in specific regions. We also investigated the traversal of GHSR over a rugged energy landscape via principal component analysis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Emma Mulry, Arka Prabha Ray, Matthew T. Eddy
Summary: Research found that under specific culture conditions, the expression yield of human histamine H-1 receptor (H1R) in methylotrophic yeast was increased by tenfold, and it responded to known H1R ligands.
Review
Biochemistry & Molecular Biology
Koh Takeuchi, Yutaka Kofuku, Shunsuke Imai, Takumi Ueda, Yuji Tokunaga, Yuki Toyama, Yutaro Shiraishi, Ichio Shimada
Summary: Multi-spanning membrane proteins transfer information and materials through a membrane by changing their conformations, and their dynamics are closely related to their function. NMR reveals dynamics information that can discriminate function-related dynamics from random fluctuations. Studies using solution NMR have contributed to revealing the structural basis of the function of multi-spanning membrane proteins.
Article
Biochemistry & Molecular Biology
Christian Baumann, Wan-Chin Chiang, Renato Valsecchi, Simon Jurt, Mattia Deluigi, Matthias Schuster, Karl Johan Rosengren, Andreas Pluckthun, Oliver Zerbe
Summary: This study investigates the rapid side-chain dynamics of a thermostabilized alpha(1B)-adrenergic receptor (alpha(1B)-AR) using methyl relaxation. The results show that the overall side-chain dynamics of the receptor are similar regardless of the ligands, but the allosteric ligand increases the flexibility of specific residues, suggesting differences in the inactivation mechanisms of orthosteric and allosteric receptors. Additionally, residues closer to the center of the membrane bilayer exhibit increased side-chain rigidity.
Article
Biochemistry & Molecular Biology
Christian Baumann, Wan-Chin Chiang, Renato Valsecchi, Simon Jurt, Mattia Deluigi, Matthias Schuster, Karl Johan Rosengren, Andreas Pluckthun, Oliver Zerbe
Summary: This study investigates the rapid side-chain dynamics of an alpha(1B)-adrenergic receptor using methyl relaxation. The results show that the overall side-chain dynamics of the receptor are similar in the presence of different ligands. However, the allosteric ligand increases the flexibility of certain key residues, suggesting differences in the mechanisms for receptor activation. These findings demonstrate the feasibility of studying receptor-wide side-chain dynamics in GPCRs to gain functional insights.
Article
Optics
Yanyu Guo, Jiayu Deng, Jiapo Li, Jun Zhou, Di Cai, Zichun Le
Summary: A study developed an effective method based on liquid light guides to suppress laser speckle, with numerical simulations showing the dependence of speckle contrast and efficiency on different liquid core types in the guides.
Article
Multidisciplinary Sciences
Inokentijs Josts, Katharina Veith, Vincent Normant, Isabelle J. Schalk, Henning Tidow
Summary: The study reported the crystal structure of the inner membrane protein FoxB, revealing its mechanism in Fe-siderophore uptake. Through in vitro assays and in vivo studies, the results establish FoxB as an inner membrane reductase involved in releasing iron from ferrioxamine during Fesiderophore uptake.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Nanoscience & Nanotechnology
Jun Ye, Renjie Li, Jialing Cheng, Dongdong Liu, Yanfang Yang, Hongliang Wang, Xiaoyan Xu, Lin Li, Panpan Ma, Yuling Liu
Summary: This study compares the colloidal stability of commercial AmB nanoformulations and finds that AmB-CSC and AmB-Lipo exhibit good colloidal stability in the injection medium, leading to reduced cytotoxicity and nephrotoxicity.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Article
Instruments & Instrumentation
D. Kushnir, N. Beyer, E. Bartsch, P. Hebraud
Summary: A wide angle static and dynamic light scattering setup was developed and characterized for studying the structure and dynamics of soft materials systems under shear conditions. The apparatus demonstrated capabilities to measure the evolution of structure factor peaks and velocity profiles in concentrated suspensions of spherical particles under shear flow. Theoretical treatment of light scattering under flow, considering Gaussian characteristics of optical paths, was compared with experimental measurements.
REVIEW OF SCIENTIFIC INSTRUMENTS
(2021)
Article
Biochemical Research Methods
Takumi Ueda, Shunsuke Imai, Ichio Shimada
Summary: GPCRs are important receptors for neurotransmitters and hormones, and they are targeted by a significant number of modern drugs. Although the number of GPCR crystal structures has increased rapidly, they alone cannot fully explain the key features of GPCR signaling. Recent studies have shown that GPCRs are structurally dynamic and can adopt multiple conformations. NMR methods provide valuable insights into the dynamics of GPCRs in solution, despite the challenges posed by their instability and large molecular weights.
JOURNAL OF MAGNETIC RESONANCE
(2022)
Article
Mechanics
Shigeki Yashiro, Tomohiro Yamasaki, Hiroto Nagai, Akinori Yoshimura
Summary: The study conducted an elastoplastic finite-element analysis on a new quasi-static mode II interlaminar fracture toughness test, the DENT test, to investigate the difference between the perceived energy release rate and the J-integral. It was found that the size of the plastic zone at the delamination crack tip played a significant role in the difference between the energy release rate and J-integral, and the difference in the DENT test was smaller compared to flexure-type tests. Compliance calibration method was applied to reduce the evaluation difference of the energy release rate in the elastoplastic analysis results of the DENT test.
ENGINEERING FRACTURE MECHANICS
(2021)
Article
Materials Science, Multidisciplinary
Ryan A. Fair, Renxuan Xie, Youngmin Lee, Ralph H. Colby, Enrique D. Gomez
Summary: Molecular weight is a critical parameter for polymers, especially conjugated polymers, often measured using gel permeation chromatography (GPC). Due to mismatch in chain flexibilities between samples and standards, as well as poor solubility in the mobile phase, inaccuracies in GPC measurements of conjugated polymers are common. By applying a universal calibration method and in-line concentration measurements, accurate results for polymers of various stiffnesses can be obtained, with the accuracy verified using absolute molecular weights from static light scattering. Measuring the refractive index increment is crucial for confirming full recovery of the polymer and ensuring accurate values of absolute molecular weight from GPC.
ACS APPLIED POLYMER MATERIALS
(2021)
Article
Polymer Science
Roman Solovov, Anfisa Kazberova, Boris Ershov
Summary: The molar mass of nitrocellulose was successfully determined using the dynamic light scattering method. The methodology for fractionating nitrocellulose in acetonic solutions and obtaining six polymer fractions with monomodal distribution is described. It was found that the unfractionated colloxylin had a polymodal molar mass distribution, with mass average molecular mass values of 87.3 +/- 14.1, 28.3 +/- 7.3, and 0.54 +/- 0.17 kDa when investigated by the dynamic light scattering method. The viscometric method provided an integral viscosity average molar mass of 56.7 +/- 5.8 kDa.
Article
Chemistry, Physical
Hai Zhu, Hao Fu, Pengfei Yan, Xue Li, Lin Zhang, Xiaomi Wang, Chengwen Chai
Summary: In this study, FT-IR and Raman techniques were used to characterize the oxygen-containing bonds in GMZ bentonite, and static multiple light scattering techniques were used to monitor the natural release process of GMZ bentonite colloids in real-time. The effect of different conditions on the generation of GMZ bentonite colloids was also investigated. The results contribute to a better understanding of bentonite erosion in different environments and the mechanism of colloid release, and provide valuable insights for the safety assessment of radioactive HLW in deep geological repositories.
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
(2022)
Article
Pharmacology & Pharmacy
Lijun Shao, Yan Chen, Shikai Zhang, Zhihui Zhang, Yongbing Cao, Dehua Yang, Ming-Wei Wang
Summary: This study comprehensively investigated the interactions between receptor activity-modulating proteins (RAMPs) and G protein-coupled receptors (GPCRs) using a bioluminescence resonance energy transfer (BRET) approach. The results revealed that RAMPs modulate the signal transduction of glucagon receptor family members in a receptor-specific manner. These findings provide new insights into the role of RAMPs in ligand recognition and receptor activation.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Clinical Neurology
Martin Flach, Cedric Leu, Alfonso Martinisi, Zhiva Skachokova, Stephan Frank, Markus Tolnay, Henning Stahlberg, David T. Winkler
Summary: This study investigated whether a non-human prion can promote the aggregation of tau protein. It was found that Sup35NM fibrils can promote tau aggregation and exacerbate tau pathology in transgenic mice. This suggests that non-mammalian prions present in the human microbiome may contribute to protein misfolding in neurodegenerative disorders.
ALZHEIMERS & DEMENTIA
(2022)
Article
Multidisciplinary Sciences
Ricardo Adaixo, Eva M. Steiner, Ricardo D. Righetto, Alexander Schmidt, Henning Stahlberg, Nicholas M. I. Taylor
Summary: This study presents the cryo-electron microscopy structure of native and fully glycosylated hTG from healthy thyroid glands, providing insights into thyroid hormonogenesis and glycosylation sites.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Pu Qian, Alastair T. Gardiner, Ivana Simova, Katerina Naydenova, Tristan Croll, Philip J. Jackson, Nupur, Miroslav Kloz, Petra Cubakova, Marek Kuzma, Yonghui Zeng, Pablo Castro-Hartmann, Bart van Knippenberg, Kenneth N. Goldie, David Kaftan, Pavel Hrouzek, Jan Hajek, Jon Agirre, C. Alistair Siebert, David Bina, Kasim Sader, Henning Stahlberg, Roman Sobotka, Christopher J. Russo, Tomas Polivka, C. Neil Hunter, Michal Koblizek
Summary: Phototrophic Gemmatimonadetes have evolved the ability to use solar energy through horizontal gene transfer. The study reveals the unique solar energy harvesting and trapping architecture of Gemmatimonas phototrophica, as well as the flow of energy within the complex.
Article
Biology
Jamie S. Depelteau, Ludovic Renault, Nynke Althof, C. Keith Cassidy, Luiza M. Mendonca, Grant J. Jensen, Guenter P. Resch, Ariane Briegel
Summary: Depelteau et al. present a new method to inactivate cryo-EM samples from pathogenic organisms using ultraviolet-C radiation in cryogenic conditions, with no discernable structural impact. This research demonstrates the effectiveness and cost-effectiveness of UVC treatment in cryo-EM sample preparation, which is important for studying the structure and function of pathogens.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Mathieu Botte, Dongchun Ni, Stephan Schenck, Iwan Zimmermann, Mohamed Chami, Nicolas Bocquet, Pascal Egloff, Denis Bucher, Matilde Trabuco, Robert K. Y. Cheng, Janine D. Brunner, Markus A. Seeger, Henning Stahlberg, Michael Hennig
Summary: Researchers report the structure of a partially opened LptDE transporter and its complex with rigid chaperones derived from nanobodies. The study provides insights into the mechanism of LPS insertion, offers a structural framework for the development of antibiotics targeting LptD, and describes a highly rigid chaperone scaffold for structural biology research on challenging protein targets.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Roman Koning, Hildo Vader, Martijn van Nugteren, Peter A. Grocutt, Wen Yang, Ludovic L. R. Renault, Abraham J. Koster, Arnold C. F. Kamp, Michael Schwertner
Summary: This article presents a vitrification device for cryo-electron microscopy, which allows automated sample handling and enables the preparation and inspection of thin film samples. The quality of the prepared samples can be characterized before data acquisition.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Valerie Biou, Ricardo Jorge Diogo Adaixo, Mohamed Chami, Pierre-Damien Coureux, Benoist Laurent, Veronique Yvette Ntsogo Enguene, Gisele Cardoso de Amorim, Nadia Izadi-Pruneyre, Christian Malosse, Julia Chamot-Rooke, Henning Stahlberg, Philippe Delepelaire
Summary: The cryo-EM structures of the ExbB and ExbB-ExbD membrane protein complexes in Serratia marcescens provide insights into the inner membrane machinery and specific interactions related to the Has system. The study reveals that ExbB(Sm) interacts with HasB through its periplasmic extension, and this interaction is involved in heme acquisition. Key residues in the membrane domain of ExbB(Sm) and ExbB(Ec) play an essential role in function and likely participate in the interaction with TonB/HasB. This research sheds light on the inner membrane energy machinery formed by ExbB, ExbD, and HasB.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chunyi Hu, Dongchun Ni, Ki Hyun Nam, Sonali Majumdar, Justin McLean, Henning Stahlberg, Michael P. Terns, Ailong Ke
Summary: This study reveals the collaborative function of type I-A Cascade and Cas3, and provides cryo-EM snapshots of the effector complex during DNA recognition and degradation. The study also discovers the autoinhibition of Cas3's HD nuclease inside the effector complex, which is allosterically activated upon full R-loop formation validated by the RNA guide. These findings inspire the conversion of Pfu Cascade-Cas3 into a nucleic acid detection tool and allele-specific inactivation editing for disease-causing mutations.
Article
Microbiology
Craig Fenwick, Priscilla Turelli, Dongchun Ni, Laurent Perez, Kelvin Lau, Cecile Herate, Romain Marlin, Erica Lana, Celine Pellaton, Charlene Raclot, Line Esteves-Leuenberger, Jeremy Campos, Alex Farina, Flurin Fiscalini, Nathalie Dereuddre-Bosquet, Francis Relouzat, Rana Abdelnabi, Caroline S. Foo, Johan Neyts, Pieter Leyssen, Yves Levy, Florence Pojer, Henning Stahlberg, Roger LeGrand, Didier Trono, Giuseppe Pantaleo
Summary: A monoclonal antibody named P2G3 isolated from a previously infected vaccinated donor shows strong neutralizing activity against the SARS-CoV-2 Omicron variant and provides complete prophylactic or therapeutic protection when used alone or in combination with another antibody. The unique epitope of P2G3 may have important implications for combating the Omicron variant.
NATURE MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Babatunde Ekundayo, Davide Torre, Bertrand Beckert, Sergey Nazarov, Alexander Myasnikov, Henning Stahlberg, Dongchun Ni
Summary: The CRISPR-guided caspase (Craspase) complex consists of Cas7-11, CRISPR RNA (crRNA), and TPR-CHAT protein. It shows potential as a tool for gene therapy and biomedical research, but its regulation is not well understood. In this study, cryoelectron microscopy was used to determine the structures of the Dm Craspase complex to understand its regulation mechanism. It was found that DmTPR-CHAT stabilizes crRNA-bound DmCas7-11 in a closed conformation through interactions mediated by DmTPR-CHAT N-terminal domain, DmCas7-11 insertion finger, and Cas11-like domain, resulting in reduced target RNA accessibility and cleavage.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Correction
Biology
Valerie Biou, Ricardo Jorge Diogo Adaixo, Mohamed Chami, Pierre-Damien Coureux, Benoist Laurent, Veronique Yvette Ntsogo Enguene, Gisele Cardoso de Amorim, Nadia Izadi-Pruneyre, Christian Malosse, Julia Chamot-Rooke, Henning Stahlberg, Philippe Delepelaire
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Pablo Gainza, Sarah Wehrle, Alexandra Van Hall-Beauvais, Anthony Marchand, Andreas Scheck, Zander Harteveld, Stephen Buckley, Dongchun Ni, Shuguang Tan, Freyr Sverrisson, Casper Goverde, Priscilla Turelli, Charlene Raclot, Alexandra Teslenko, Martin Pacesa, Stephane Rosset, Sandrine Georgeon, Jane Marsden, Aaron Petruzzella, Kefang Liu, Zepeng Xu, Yan Chai, Pu Han, George F. Gao, Elisa Oricchio, Beat Fierz, Didier Trono, Henning Stahlberg, Michael Bronstein, Bruno E. Correia
Summary: Physical interactions between proteins are crucial for biological processes. A geometric deep-learning framework is used to generate fingerprints on protein surfaces to describe the key aspects of molecular recognition. Using this approach, several de novo protein binders were designed and successfully bound to different protein targets.
Article
Multidisciplinary Sciences
Galina Limorenko, Meltem Tatli, Rajasekhar Kolla, Sergey Nazarov, Marie-Theres Weil, David C. Schondorf, Daniela Geist, Peter Reinhardt, Dagmar E. Ehrnhoefer, Henning Stahlberg, Laura Gasparini, Hilal A. Lashuel
Summary: The authors present a method to produce co-factor-free fibrils from all full-length Tau isoforms, which allows for the reconstitution of pathology resembling Tau fibrils and the screening of Tau aggregation-modifying compounds for targeted therapies and PET tracers.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Dongchun Ni, Xuhang Lu, Henning Stahlberg, Babatunde Ekundayo
Summary: Short prokaryotic argonaute (pAgo) and toll/interleukin-1 receptor/resistance protein (TIR)-analog of PAZ (APAZ) form a heterodimeric SPARTA complex that provides immunity to its prokaryotic host through an abortive infection mechanism. Monomeric SPARTA senses foreign RNA/DNA duplexes to assemble an active tetramer resulting in cell death by NAD depletion via an unknown mechanism. Our findings provide detailed structural and mechanistic insights into activating a short argonaute defense system.
Meeting Abstract
Biochemistry & Molecular Biology
Alexandra Van Hall-Beauvais, Pablo Gainza, Sarah Wehrle, Andreas Scheck, Anthony Marchand, Zander Harteveld, Casper Goverde, Dongchun Ni, Tan Shuguang, Priscilla Turelli, Didier Trono, Henning Stahlberg, Geroge Gao, Michael Bronstein, Bruno Correia