Article
Biology
Alexander S. Hauser, Charlotte Avet, Claire Normand, Arturo Mancini, Asuka Inoue, Michel Bouvier, David E. Gloriam
Summary: Two-thirds of human hormones and one-third of clinical drugs act on membrane receptors coupled to G proteins, but there are differences in the reported G protein couplings among recent large-scale datasets. This study presents a common coupling map that uncovers novel couplings, GPCR-G protein selectivity, and the comparison of co-coupling and co-expression of G proteins with phylogenetic relationships. These findings will advance receptor research and cellular signaling, and contribute to the development of safer drugs.
Review
Biochemistry & Molecular Biology
Raudah Lazim, Donghyuk Suh, Jai Woo Lee, Thi Ngoc Lan Vu, Sanghee Yoon, Sun Choi
Summary: The presence of GPCR dimers has sparked research into their importance in disease pathogenesis and drug design, uncovering new signaling pathways and potential therapeutic targets. The increasing influence of computational methods in research is providing new avenues for understanding the functions and interactions of GPCRs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Mitchell Bruederlin, Raphael Boehm, Firas Fadel, Sebastian Hiller, Tilman Schirmer, Badri N. Dubey
Summary: In two-component systems, histidine kinases (HKs) relay information to response regulators (RRs) by transferring the phosphoryl group from HK to RR's Rec domain. Multi-step phosphorelays involve an additional Rec (Rec(inter)) domain in HK that acts as an intermediary for phosphoryl shuttling. This study focuses on the Rec(inter) domain of the hybrid HK CckA and reveals that it does not undergo structural changes upon pseudo-phosphorylation, unlike the well-studied homologs in response regulators.
NATURE COMMUNICATIONS
(2023)
Article
Microbiology
Peng-Peng Wang, Xuefeng Jiang, Liying Zhu, Dan Zhou, Mingyang Hong, Lu He, Lumeng Chen, Shijie Yao, Yan Zhao, Guang Chen, Chengqi Wang, Liwang Cui, Yaming Cao, Xiaotong Zhu
Summary: GPR180 is involved in signal transduction during gametogenesis in malaria parasites and its deletion impairs gametogenesis and reduces transmission to mosquitoes.
MICROBIOLOGY SPECTRUM
(2022)
Article
Biochemistry & Molecular Biology
Takeshi Hayashi, Lay Katoh, Fumiyo Ozoe, Yoshihisa Ozoe
Summary: Studies on 13 heterocyclic OAR agonists suggest structure-dependent receptor subtype selectivity and G protein subtype preference, emphasizing the importance of determining which subtype and signaling pathway mediates toxicologically relevant effects. Insecticidal assays using B. mori larvae indicate that the activation of signal transduction pathways via alpha-ALOARs may be primarily responsible for the toxicological effects of heterocycles.
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Argha Mitra, Arijit Sarkar, Marton Richard Szabo, Attila Borics
Summary: Recent advancements in experimental structural biology have provided high-resolution structures of G protein-coupled receptors, shedding light on the mechanisms of transition between active and inactive states. Molecular dynamics simulations demonstrate that external stimulus transmission to the intracellular surface of the receptor involves subtle movements of polar amino acid side chains.
Article
Plant Sciences
Jun Takeuchi, Kosuke Fukui, Yoshiya Seto, Yousuke Takaoka, Masanori Okamoto
Summary: Small-molecule plant hormones play a crucial role in controlling plant growth, development, differentiation, and environmental responses. Through genomic decoding of model plants with genetic mutants, scientists have elucidated the molecular mechanisms of nine types of plant hormones and identified the structure of hormone receptors. Studies on the three-dimensional structure of ligand-receptor complexes have revealed the details of ligand perception mechanisms.
Review
Plant Sciences
Yijie Wang, Jose Ramon Botella
Summary: As sessile organisms, plants have evolved mechanisms to adapt to environmental fluctuations. Heterotrimeric G proteins play essential roles in the response to stress in plants, regulating multiple signaling pathways. Understanding the functions of G proteins in stress reactions can contribute to the development of resilient crops and global food security.
Review
Biochemistry & Molecular Biology
Hao Chen, Suli Zhang, Ruiqi Hou, Huirong Liu
Summary: This review summarizes the discovery of the beta(1)-AR-Gi pathway and its significance in the treatment of heart diseases.
ACTA BIOCHIMICA ET BIOPHYSICA SINICA
(2022)
Article
Chemistry, Multidisciplinary
Hanrui Liu, Toni A. Baeumler, Kai Nakamura, Yuga Okada, Seojung Cho, Akihiro Eguchi, Daisuke Kuroda, Kouhei Tsumoto, Ryosuke Ueki, Shinsuke Sando
Summary: Cell membrane receptors play a crucial role in regulating cellular responses by detecting and transducing extracellular signals. Receptor engineering allows for directing cells to respond to specific external cues and perform programmed functions. This study introduces an aptamer-based signal transduction system that enables control and customization of engineered receptor functions.
Review
Biochemistry & Molecular Biology
Roberto Maggio, Irene Fasciani, Marco Carli, Francesco Petragnano, Francesco Marampon, Mario Rossi, Marco Scarselli
Summary: The passage discusses the importance of information exchange and interpretation in biology, particularly in how cells integrate signals from various molecules. G protein-coupled receptors (GPCRs) play a crucial role in signal recognition and transduction within cells, and their formation of higher order oligomers helps organize cell compartments along the membrane. This structural basis allows for cells to perceive and discriminate localized increases in second messengers, contributing to the understanding of physiological roles played by receptor homo- and hetero-oligomerization in cell biology.
Review
Endocrinology & Metabolism
Morris F. White, C. Ronald Kahn
Summary: The discovery and application of insulin marked a major turning point in medical history, playing a crucial role in blood glucose regulation and the treatment of diseases like diabetes.
MOLECULAR METABOLISM
(2021)
Article
Multidisciplinary Sciences
Moon Young Yang, Soo-Kyung Kim, William A. Goddard
Summary: In this study, the authors predict the mechanism by which the inactive G protein induces conformational changes in the GABA(B) receptor to form an intermediate state.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Edward Hartsough, Rajani R. J. Shelke, Razie Amraei, Zahra Aryan, Saran Lotfollahzadeh, Nader Rahimi
Summary: Activation and signal transduction of vascular endothelial growth factor receptor-2 (VEGFR-2) play crucial roles in vasculogenesis and pathological angiogenesis. The study reveals that protein arginine methyltransferase 4 (PRMT4) mediates methylation of a specific site on VEGFR-2, which affects VEGFR-2-induced angiogenic responses. This finding may have implications for the development of targeted VEGFR-2 inhibitors.
Review
Engineering, Biomedical
Yuhong Jiang, Yuke Li, Xiujuan Fu, Yue Wu, Rujing Wang, Mengnan Zhao, Canquan Mao, Sanjun Shi
Summary: The translation article introduces the interaction between G protein-coupled receptors (GPCRs) and nanotechnology, as well as how nanotechnology can improve the efficacy and safety of GPCR-related drugs. Nanotechnology can encapsulate GPCR ligands to construct synthetic nano-GPCRs and precisely initiate sustained endosomal signal transduction through nanoparticles. Moreover, nanoparticles can enhance the potency of delivery systems by actively targeting specific cells through ligand-receptor binding and receptor-dependent endocytosis.
ACTA BIOMATERIALIA
(2023)
Article
Pharmacology & Pharmacy
David Speck, Gunnar Kleinau, Mark Meininghaus, Antje Erbe, Alexandra Einfeldt, Michal Szczepek, Patrick Scheerer, Vera Puetter
Summary: G-protein coupled receptors (GPCR) play a crucial role in transducing extracellular stimuli into cells, making them an important target in medical and pharmacological research. However, the expression and purification of these receptors have remained challenging due to their specificities and the need for appropriate experimental conditions. In this study, the expression and purification of a specific GPCR (RXFP1) were described, and various constructs were designed for functional and structural studies. The results may support further research on RXFP1 receptors, such as small molecule ligand screening or structural elucidation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Aurelie Philippe, Gunnar Kleinau, Jason Jannis Gruner, Sumin Wu, Daniel Postpieszala, David Speck, Harald Heidecke, Simon J. Dowell, Gabriela Riemekasten, Peter W. Hildebrand, Julian Kamhieh-Milz, Rusan Catar, Michal Szczepek, Duska Dragun, Patrick Scheerer
Summary: This study investigates the effects of AT(1)R-Abs on G-protein signaling and cell proliferation, as well as the involvement of extracellular receptor loops. The results show that AT(1)R-Abs activate G(q/11) signaling, leading to cell proliferation and inhibiting receptor internalization. Additionally, ligand-independent activation of G(i) signaling by AT(1)R has a negative effect on cell proliferation. The study also identifies the involvement of certain extracellular receptor loops in the interaction between AT(1)R and antibodies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Yang Yang, Till Stensitzki, Luisa Sauthof, Andrea Schmidt, Patrick Piwowarski, Francisco Velazquez Escobar, Norbert Michael, Anh Duc Nguyen, Michal Szczepek, Florian Nikolas Brunig, Roland Rudiger Netz, Maria Andrea Mroginski, Suliman Adam, Franz Bartl, Igor Schapiro, Peter Hildebrandt, Patrick Scheerer, Karsten Heyne
Summary: The biological function of phytochromes is triggered by the photoisomerization of the chromophore. Proton-coupled dynamics in the excited state of phytochromes lead to structural changes in the protein, activating its function. This study provides insights into the mechanism of protein activation in phytochromes.
Review
Endocrinology & Metabolism
David Speck, Gunnar Kleinau, Michal Szczepek, Dennis Kwiatkowski, Rusan Catar, Aurelie Philippe, Patrick Scheerer
Summary: Angiotensin and endothelin receptors are important therapeutic targets for various diseases and conditions. Autoantibodies can activate these receptors and lead to disease symptoms. The exact differences between autoantibodies and endogenous ligands in receptor binding and activation are still not well understood. Recent structural studies using X-ray crystallography have provided important information for understanding the properties of these receptors and developing pharmacological strategies.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Multidisciplinary Sciences
Katarina Nemec, Hannes Schihada, Gunnar Kleinau, Ulrike Zabel, Eugene O. Grushevskyi, Patrick Scheerer, Martin J. Lohse, Isabella Maiellaro
Summary: This study discovered that receptor-activity-modifying protein 2 (RAMP2) acts as a specific allosteric modulator of parathyroid hormone 1 receptor (PTH1R), shifting it to a preactivated state and affecting its downstream signaling. These findings provide a new avenue for modulating GPCR function and drug design.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Nanina Reininghaus, Sarah Paisdzior, Friederike Hoepfner, Sabine Jyrch, Cigdem Cetindag, Patrick Scheerer, Peter Kuhnen, Heike Biebermann
Summary: In this study, the effects of inhibiting homodimerization on G(q/11) signaling were analyzed using chimeric receptors. The results show that inhibiting homodimerization has a setmelanotide-like effect on G(q/11) signaling, with chimeric receptors presenting increased potency compared to wild-type MC4R. These findings indicate the potential of inhibiting MC4R homodimerization as a therapeutic target to treat obesity.
Article
Rheumatology
Bjoern Hegner, Tobias Kretzschmar, Nan Zhu, Gunnar Kleinau, Hongfan Zhao, Julian Kamhieh-Milz, Julia Hilger, Ralf Schindler, Patrick Scheerer, Gabriela Riemekasten, Aurelie Philippe, Rusan Catar
Summary: This study provides experimental evidence that activating autoantibodies may contribute to scleroderma renal crisis (SRC). This effect is likely related to direct receptor stimulation and additional allosteric effects. Novel therapies targeting autoimmune hyperactivation of the angiotensin II type 1 receptor (AT(1)R) and the endothelin-1 type A receptor (ETAR) may improve outcomes in severe cases of SRC.
Article
Multidisciplinary Sciences
Amadeus Samuel Schulze, Gunnar Kleinau, Rosanna Krakowsky, David Rochmann, Ranajit Das, Catherine L. Worth, Petra Krumbholz, Patrick Scheerer, Claudia Staeubert
Summary: G protein-coupled receptor 84 (GPR84) is an immune cell receptor whose expression is increased under inflammatory conditions. Through the analysis of vertebrate genome data, we found that GPR84 has been present in vertebrates for a long time but is absent in birds. Positive selection evidence was found in certain mammalian GPR84 orthologs, and naturally occurring human GPR84 variants were identified to cause loss of function. Additionally, we discovered two highly conserved ligands that mediate bacterial communication.
Article
Biophysics
Abhishek Acharya, Kalyanashis Jana, Dominik Gurvic, Ulrich Zachariae, Ulrich Kleinekathofer
Summary: Predicting molecular permeability and evaluating the effect of molecular transformations on permeation rates are critical for the development of effective antibiotics. In this study, a computational approach using Brownian dynamics is proposed to obtain estimates of molecular permeability through a porin channel within hours. The method is significantly faster compared with previous approaches and shows good correlation with experimental results. The potential applications of this method in high-throughput screening for fast permeators are discussed.
BIOPHYSICAL JOURNAL
(2023)
Article
Physiology
Callum M. M. Ives, Neil J. J. Thomson, Ulrich Zachariae
Summary: Selective ion exchange across cellular membranes is important for cellular processes, especially Ca2+-mediated signaling. Maintaining strict Ca2+ concentration gradients across membranes is necessary due to the cytotoxic nature of elevated intracellular Ca2+ levels. The TRPV ion channels, particularly TRPV5 and TRPV6, play a crucial role in Ca2+ signaling by allowing selective permeation of Ca2+ ions. This study uses molecular dynamics simulations to investigate the mechanisms behind the high Ca2+ selectivity of some TRPV channels compared to others.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Bo Qin, Simon M. M. Lauer, Annika Balke, Carlos H. H. Vieira-Vieira, Jorg Buerger, Thorsten Mielke, Matthias Selbach, Patrick Scheerer, Christian M. T. Spahn, Rainer Nikolay
Summary: Ribosome biogenesis is a multi-step cellular process that involves the production, processing, folding, and modification of ribosomal RNAs (rRNAs) and ribosomal proteins. By using a minimal in vitro reconstitution system, researchers studied the early assembly phase of the bacterial 50S subunit and found that it occurs in a domain-wise fashion, with late assembly proceeding incrementally. The study also showed that ribosomal proteins and folded rRNA helices induce or stabilize rRNA folds within adjacent regions, creating cooperativity.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Yvonne Giesecke, Vahid Asimi, Valentina Stulberg, Gunnar Kleinau, Patrick Scheerer, Beate Koksch, Carsten Grotzinger
Summary: No experimental evidence was found to support a role of PEN as a GPR83 ligand, and there are conflicting reports on the binding and activation of GPR83 by PEN.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Gunnar Kleinau, Amal Hassan Ali, Franziska Wiechert, Michal Szczepek, Andrea Schmidt, Christian M. T. Spahn, Ines Liebscher, Torsten Schoeneberg, Patrick Scheerer
Summary: Adhesion G protein-coupled receptors (aGPCRs), specifically class B2 known as aGPCRs, have gained increasing research attention due to their physiological role as mechano-sensors in cell-cell and cell-matrix contexts. The identification of the Stachel sequence has advanced our understanding of signal transduction in aGPCRs, and recent structural studies have provided new insights into the architecture and molecular function of this receptor class.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Afaf Elkurdi, Gernot Guigas, Latifa Hourani-Alsharafat, Patrick Scheerer, Gerd Ulrich Nienhaus, Norbert Krauss, Tilman Lamparter
Summary: Phytochromes are photoreceptor proteins that can convert between two different forms, Pr and Pfr. The N-terminal photosensory chromophore module (PCM), composed of PAS, GAF, and PHY domains, and the C-terminus histidine kinase module play important roles in this process. By studying Agp1 mutants, researchers found a mechanical coupling between position 362 and the histidine kinase, and flexibility around position 308 in both Pr and Pfr forms.
PHOTOCHEMISTRY AND PHOTOBIOLOGY
(2023)
Article
Plant Sciences
Julia Smirnova, Justus Loerke, Gunnar Kleinau, Andrea Schmidt, Joerg Buerger, Etienne H. Meyer, Thorsten Mielke, Patrick Scheerer, Ralph Bock, Christian M. T. Spahn, Reimo Zoschke
Summary: Translation in plant cells occurs in three compartments, and this study focuses on the structure of the 80S ribosomes in the cytosol. By using cryo-electron microscopy, the researchers solved the structure of translating tobacco ribosomes and gained insights into the molecular underpinnings of cytosolic translation in plants.