Article
Pharmacology & Pharmacy
Sam Groom, Nina K. Blum, Alexandra E. Conibear, Alexander Disney, Rob Hill, Stephen M. Husbands, Yangmei Li, Lawrence Toll, Andrea Kliewer, Stefan Schulz, Graeme Henderson, Eamonn Kelly, Chris P. Bailey
Summary: This study confirmed that Compound 1 is a G protein-biased mu agonist that can induce substantial rapid receptor desensitisation in mammalian neurons. However, contrary to previous assumptions, the desensitisation effect of Compound 1 is dependent on G protein-coupled receptor kinase (GRK).
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shuai Luo, Peng Zhang, Wei Miao, Jie Xiong
Summary: This study provides the first comprehensive genome-wide identification of GPCRs in ciliates, identifying 492 GPCRs in 24 ciliates. GPCRs in ciliates can be assigned to four families, with most belonging to family A. Gene duplication events play a role in the expansion of the GPCR superfamily in ciliates. This study improves our understanding of the evolution and function of GPCRs in ciliates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nicole Ahrens, Dana Elbers, Helena Greb, Ulrike Janssen-Bienhold, Karl-Wilhelm Koch
Summary: The study revealed diverse properties of recoverin and opsin kinase in zebrafish retina due to differential expression and interaction profiles, indicating distinct roles of different recoverin paralogs in rod and cone cells.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Review
Biology
Terry W. Moody, Irene Ramos-Alvarez, Robert T. Jensen
Summary: Cancer growth is regulated by receptor tyrosine kinases (RTKs) and G-protein-coupled receptors (GPCRs). Different mutations in EGFR and NTSR1 can lead to abnormal cancer proliferation. The use of tyrosine kinase inhibitors and SR48692 as antagonists can impair the transactivation process and inhibit cancer growth.
Article
Biochemistry & Molecular Biology
Damian Jacenik, Pawel Hikisz, Ellen J. Beswick, Jakub Fichna
Summary: Among the various adhesion G protein-coupled receptors, ADGRF5 stands out with its unique domains in the N-terminal tail that play a critical role in cell-cell and cell-matrix interactions, as well as cell adhesion. Although the biology of ADGRF5 is still not fully understood, accumulating evidence suggests its fundamental importance in both health and disease. Recent studies have highlighted its potential diagnostic value in osteoporosis and cancers, and ongoing research indicates its relevance to other diseases as well. This article provides a comprehensive overview of the current understanding of ADGRF5 in human disease physiology and pathophysiology, emphasizing its potential as a novel therapeutic target in various areas.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Biochemistry & Molecular Biology
Sandra Berndt, Ines Liebscher
Summary: SFKs are crucial regulators of cell proliferation, differentiation, and survival, with their expression strongly linked to cancer development and tumor progression. The regulation of SFKs through GPCR-mediated pathways is complex and may involve direct protein interactions or allosteric regulation by arrestins and G proteins. The potential direct interaction between GPCRs and SFKs could lead to a novel mechanism of SFK signaling and identification of new GPCR-SFK interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Haoran Jiang, Daniella Galtes, Jialu Wang, Howard A. Rockman
Summary: This review explores the signaling pathways, dynamic structures, and physiological relevance of the three most important GPCR signaling effectors in the cardiovascular system: heterotrimeric G proteins, GPCR kinases (GRKs), and 8-arrestins. It summarizes their prominent roles in GPCR pharmacology before transitioning into less well-explored areas. The application of new technologies has contributed to an increasing understanding of GPCR structure and downstream effectors.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Pharmacology & Pharmacy
Alastair C. Keen, Manuela Jorg, Michelle L. L. Halls
Summary: The ubiquitin-proteasome system is a major pathway for protein degradation in cells, and methods have been developed to exploit this system for targeted protein degradation. Targeted protein degraders have been useful tools in discovery research and are being developed as therapeutics. However, most targeted protein degrader technologies have been developed for cytosolic proteins, while examples for G protein-coupled receptor (GPCR) degradation are limited. This review discusses the strategies used for applying targeted protein degradation to GPCRs and explores alternative approaches used for degrading other integral membrane proteins.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
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)
Review
Biochemistry & Molecular Biology
Roberto Maggio, Irene Fasciani, Francesco Petragnano, Maria Francesca Coppolino, Marco Scarselli, Mario Rossi
Summary: Unstructured regions in functional proteins, specifically the i3 loop and C-terminus in G protein-coupled receptors (GPCRs), have been recognized as crucial elements in GPCR function and regulation. They play critical roles in allosterically regulating GPCR activation, as autoregulators in receptor coupling specificity, and in facilitating receptor stability and interactions with intracellular protein partners.
Article
Pharmacology & Pharmacy
Estefania Moreno, Nil Casajuana-Martin, Michael Coyle, Baruc Campos Campos, Ewa Galaj, Claudia Llinas del Torrent, Arta Seyedian, William Rea, Ning-Sheng Cai, Alessandro Bonifazi, Benjamin Floran, Zheng-Xiong Xi, Xavier Guitart, Vicent Casado, Amy H. Newman, Christopher Bishop, Leonardo Pardo, Sergi Ferre
Summary: This study provides evidence that heteromerization of G protein-coupled receptors (GPCRs), specifically dopamine D1 and D3 receptors, can influence the pharmacological properties of selective ligands. In vivo experiments support the involvement of D1R-D3R heteromers in the development of L-DOPA-induced dyskinesia in Parkinson's disease, suggesting the potential of targeting GPCR heteromers for drug development.
PHARMACOLOGICAL RESEARCH
(2022)
Article
Multidisciplinary Sciences
Vaithish Velazhahan, Ning Ma, Gaspar Pandy-Szekeres, Albert J. Kooistra, Yang Lee, David E. Gloriam, Nagarajan Vaidehi, Christopher G. Tate
Summary: GPCRs are divided into six classes, with structures of vertebrate GPCRs well understood but not of fungal class D GPCRs. This study reveals the structure of a class D GPCR in yeast and its coupling to G proteins, providing a template for the design of drugs to treat fungal diseases.
Article
Biochemistry & Molecular Biology
Juergen Einsiedel, Maximilian F. Schmidt, Harald Huebner, Peter Gmeiner
Summary: A broadly applicable synthesis method was developed for peptides incorporating mixed disulfides between cysteine and homocysteine and cysteamine. The method was successfully applied to pharmacologically relevant GPCR ligands and showed covalent binding to neurotensin receptor 1 in a radioligand depletion study.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Developmental Biology
Farah Saad, David R. Hipfner
Summary: The Hedgehog (Hh) pathway is regulated by G protein-coupled receptors (GPCRs) in Drosophila, with Mthl5 identified as a modulator of this pathway. This suggests potential crosstalk between GPCRs and the Hh pathway in mammals as well.
Article
Pharmacology & Pharmacy
Jyrki P. Kukkonen
Summary: Recent data indicates cooperative effects between identical orthosteric binding sites in a G-protein-coupled receptor dimer. A mathematical model was created to test this concept, showing that even a neutral receptor ligand can allosterically affect agonist binding through the orthosteric binding site.
PHARMACOLOGICAL RESEARCH
(2021)
Correction
Virology
Stuart G. Siddell, Peter J. Walker, Elliot J. Lefkowitz, Arcady R. Mushegian, Bas E. Dutilh, Balazs Harrach, Robert L. Harrison, Sandra Junglen, Nick J. Knowles, Andrew M. Kropinski, Mart Krupovic, Jens H. Kuhn, Max L. Nibert, Luisa Rubino, Sead Sabanadzovic, Peter Simmonds, Arvind Varsani, Francisco Murilo Zerbini, Andrew J. Davison
ARCHIVES OF VIROLOGY
(2020)
Article
Virology
Stuart G. Siddell, Peter J. Walker, Elliot J. Lefkowitz, Arcady R. Mushegian, Bas E. Dutilh, Balazs Harrach, Robert L. Harrison, Sandra Junglen, Nick J. Knowles, Andrew M. Kropinski, Mart Krupovic, Jens H. Kuhn, Max L. Nibert, Luisa Rubino, Sead Sabanadzovic, Peter Simmonds, Arvind Varsani, Francisco Murilo Zerbini, Andrew J. Davison
ARCHIVES OF VIROLOGY
(2020)
Review
Microbiology
A. R. Mushegian
JOURNAL OF BACTERIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Arcady Mushegian, Irina Sorokina, Alexey Eroshkin, Mensur Dlakic
Article
Microbiology
Alexander E. Gorbalenya, Mart Krupovic, Arcady Mushegian, Andrew M. Kropinski, Stuart G. Siddell, Arvind Varsani, Michael J. Adams, Andrew J. Davison, Bas E. Dutilh, Balazs Harrach, Robert L. Harrison, Sandra Junglen, Andrew M. Q. King, Nick J. Knowles, Elliot J. Lefkowitz, Max L. Nibert, Luisa Rubino, Sead Sabanadzovic, Helene Sanfacon, Peter Simmonds, Peter J. Walker, F. Murilo Zerbini, Jens H. Kuhn
NATURE MICROBIOLOGY
(2020)
Article
Microbiology
Arcady R. Mushegian, Santiago F. Elena
Article
Virology
Peter J. Walker, Stuart G. Siddell, Elliot J. Lefkowitz, Arcady R. Mushegian, Evelien M. Adriaenssens, Donald M. Dempsey, Bas E. Dutilh, Balazs Harrach, Robert L. Harrison, R. Curtis Hendrickson, Sandra Junglen, Nick J. Knowles, Andrew M. Kropinski, Mart Krupovic, Jens H. Kuhn, Max Nibert, Richard J. Orton, Luisa Rubino, Sead Sabanadzovic, Peter Simmonds, Donald B. Smith, Arvind Varsani, Francisco Murilo Zerbini, Andrew J. Davison
ARCHIVES OF VIROLOGY
(2020)
Article
Virology
Peter J. Walker, Stuart G. Siddell, Elliot J. Lefkowitz, Arcady R. Mushegian, Evelien M. Adriaenssens, Poliane Alfenas-Zerbini, Andrew J. Davison, Donald M. Dempsey, Bas E. Dutilh, Maria Laura Garcia, Balazs Harrach, Robert L. Harrison, R. Curtis Hendrickson, Sandra Junglen, Nick J. Knowles, Mart Krupovic, Jens H. Kuhn, Amy J. Lambert, Malgorzata Lobocka, Max L. Nibert, Hanna M. Oksanen, Richard J. Orton, David L. Robertson, Luisa Rubino, Sead Sabanadzovic, Peter Simmonds, Donald B. Smith, Nobuhiro Suzuki, Koenraad Van Dooerslaer, Anne-Mieke Vandamme, Arvind Varsani, Francisco Murilo Zerbini
Summary: This article reports the changes to virus taxonomy approved and ratified by ICTV in March 2021. All proposals and revisions were passed by an absolute majority of ICTV members. ICTV mandated a new uniform rule for virus species naming, abolished the notion of a type species, and clarified its remit through an official definition of 'virus' and other types of mobile genetic elements.
ARCHIVES OF VIROLOGY
(2021)
Article
Virology
Francisco Murilo Zerbini, Stuart G. Siddell, Arcady R. Mushegian, Peter J. Walker, Elliot J. Lefkowitz, Evelien M. Adriaenssens, Poliane Alfenas-Zerbini, Bas E. Dutilh, Maria Laura Garcia, Sandra Junglen, Mart Krupovic, Jens H. Kuhn, Amy J. Lambert, Malgorzata Lobocka, Hanna M. Oksanen, David L. Robertson, Luisa Rubino, Sead Sabanadzovic, Peter Simmonds, Nobuhiro Suzuki, Koenraad Van Doorslaer, Anne-Mieke Vandamme, Arvind Varsani
Summary: Following the ICTV Ratification Vote in March 2021, a standard two-part binomial nomenclature is now the standard for naming virus species. The adoption of this new nomenclature is still in its early stages, making it timely to clarify the distinction between viruses and virus species and provide guidelines for their correct naming and writing.
ARCHIVES OF VIROLOGY
(2022)
Review
Plant Sciences
Olga Tsoy, Arcady Mushegian
Summary: This article mainly introduces the research on the product of the FT gene as a key component of florigen, and discusses the molecular features and functions of FT homologs, suggesting that they may act as enzymes on small molecule metabolites.
Review
Biochemistry & Molecular Biology
Irina Sorokina, Arcady R. Mushegian, Eugene V. Koonin
Summary: The prevailing thermodynamic hypothesis of protein folding is called into question due to the lack of strong empirical evidence. Physical theory-based approaches in predicting protein folds have largely failed, except for small proteins. Recent successes in protein structure prediction have been achieved through evolutionary modeling and deep learning methods, but provide no insights into protein folding mechanisms and pathways. An alternative view suggests that most proteins do not occupy the global minimum of free energy, but instead a local minimum on a fluctuating landscape. This view also argues that the majority of proteins require energy-dependent cellular processes for folding, such as interactions with the translation system and chaperones.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Peter J. Walker, Stuart G. Siddell, Elliot J. Lefkowitz, Arcady R. Mushegian, Evelien M. Adriaenssens, Poliane Alfenas-Zerbini, Donald M. Dempsey, Bas E. Dutilh, Maria Laura Garcia, R. Curtis Hendrickson, Sandra Junglen, Mart Krupovic, Jens H. Kuhn, Amy J. Lambert, Malgorzata Lobocka, Hanna M. Oksanen, Richard J. Orton, David L. Robertson, Luisa Rubino, Sead Sabanadzovic, Peter Simmonds, Donald B. Smith, Nobuhiro Suzuki, Koenraad Van Doorslaer, Anne-Mieke Vandamme, Arvind Varsani, Francisco Murilo Zerbini
Summary: This article discusses the changes in virus taxonomy approved by the International Committee on Taxonomy of Viruses (ICTV) in March 2022. The ICTV members voted on 174 taxonomic proposals, all of which were ratified by an absolute majority. The implementation of a new naming rule for virus species has resulted in over 60% of virus species being named in the 'Genus_name species_epithet' format.
ARCHIVES OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Arcady Mushegian
Summary: Methyltransferases play an important role in the interaction between viruses and eukaryotic hosts. In Riboviria, these methyltransferases have structural similarities to the widespread FtsJ/RrmJ-like methyltransferases in cells, but there are also different classes of methyltransferases. Analysis of spatial structures revealed that conserved residues play a crucial role in the catalytic mechanism. Phylogenetic evidence suggests that methyltransferases in Riboviria likely originated from cellular RrmJ-like enzymes and have undergone rapid divergence with infrequent horizontal transfer between different viruses.
Article
Virology
Francisco Murilo Zerbini, Stuart G. Siddell, Elliot J. Lefkowitz, Arcady R. Mushegian, Evelien M. Adriaenssens, Poliane Alfenas-Zerbini, Donald M. Dempsey, Bas E. Dutilh, Maria Laura Garcia, R. Curtis Hendrickson, Sandra Junglen, Mart Krupovic, Jens H. Kuhn, Amy J. Lambert, Malgorzata Lobocka, Hanna M. Oksanen, David L. Robertson, Luisa Rubino, Sead Sabanadzovic, Peter Simmonds, Donald B. Smith, Nobuhiro Suzuki, Koenraad Van Doorslaer, Anne-Mieke Vandamme, Arvind Varsani
Summary: This article reports on changes to virus taxonomy and nomenclature approved by the International Committee on Taxonomy of Viruses (ICTV) in April 2023. All ICTV members were invited to vote on 174 taxonomic proposals and a revision of the ICTV Statutes that had been approved by the ICTV Executive Committee in July 2022. Majority approval was obtained for all proposals and the revised ICTV Statutes. A significant change was the renaming of existing species according to the binomial format and the classification of gene transfer agents (GTAs) as viriforms. In total, one class, seven orders, 31 families, 214 genera, and 858 species were created.
ARCHIVES OF VIROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Harutyun Sahakyan, Karen Nazaryan, Arcady Mushegian, Irina Sorokina
Summary: Molecular dynamics simulations were performed to study protein folding. By applying rotational force to the C-terminal amino acid while restricting the movement of the N-terminal amino acid, the folding of four protein domains was accelerated at least by an order of magnitude. These results suggest that external forces and constraints can bias the motions of the polypeptide and facilitate the attainment of stable fold.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)