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.
Review
Genetics & Heredity
Abhijit Sreepada, Mansi Tiwari, Kasturi Pal
Summary: This article provides an overview of the classification of human G protein-coupled receptors (GPCRs) and the characteristics of adhesion GPCRs (aGPCRs). It discusses the crucial roles of aGPCRs in organ development, their involvement in various physiological processes, and their association with diseases.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2022)
Review
Pharmacology & Pharmacy
Ilana B. Kotliar, Emily Lorenzen, Jochen M. Schwenk, Debbie L. Hay, Thomas P. Sakmar
Summary: G protein-coupled receptors (GPCRs) interact with a variety of membrane proteins, but the extent and mechanisms of these interactions are not well understood. RAMPs, a class of GPCR-interacting proteins, have been extensively studied. Recent research suggests that GPCR-RAMP interactions may be more widespread than previously thought. This review summarizes the latest techniques for discovering GPCR-RAMP interactions and their functional consequences, and discusses future research prospects.
PHARMACOLOGICAL REVIEWS
(2023)
Review
Immunology
Nan Li, Shan Shan, Xiu-Qin Li, Ting-Ting Chen, Meng Qi, Sheng-Nan Zhang, Zi-Ying Wang, Ling-Ling Zhang, Wei Wei, Wu-Yi Sun
Summary: G protein-coupled receptor kinase 2 (GRK2) plays important roles in regulating signaling pathways associated with fibrotic diseases. Recent research suggests that GRK2 could be a potential therapeutic target for fibrotic diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Viren Patwa, Shuchi Guo, Rhonda L. Carter, Lindsay Kraus, Jeanette Einspahr, David Teplitsky, Abdelkarim Sabri, Douglas G. Tilley
Summary: The proximal region of the JMD of EGFR is responsible for its association with beta 1AR, and disruption of this interaction prevents beta 1AR-mediated transactivation, providing a new tool for studying the functional consequences of disrupting beta 1AR-EGFR downstream signaling.
CELLULAR SIGNALLING
(2021)
Article
Pharmacology & Pharmacy
Zhengnan Ren, Xiaohua Pan, Jiahong Li, Xiaoliang Dong, Xing Tu, Li Long Pan, Jia Sun
Summary: GPR41 is found to be involved in the progression of pulmonary fibrosis, and its knockout attenuates fibrosis and decreases collagen secretion. This suggests that GPR41 could be a potential therapeutic target for pulmonary fibrosis.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Chemistry, Medicinal
Alessandro Nicoli, Franziska Haag, Patrick Marcinek, Ruiming He, Johanna Kreissl, Joerg Stein, Alessandro Marchetto, Andreas Dunkel, Thomas Hofmann, Dietmar Krautwurst, Antonella Di Pizio
Summary: With approximately 400 encoding genes in humans, odorant receptors (ORs) are the largest subfamily of class A G protein-coupled receptors (GPCRs), but their structural characterization is poor. This study focuses on the characterization of the odorant receptor OR5K1 by identifying its cognate agonists and investigating its binding modes using AI-driven modeling and homology modeling. The obtained models provide insights into the differences in activity and structural variations. This refinement protocol can be applied to model the orthosteric binding site of ORs and GPCRs with low sequence identity.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
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)
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
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)
Review
Pharmacology & Pharmacy
Bui San Thai, Ling Yeong Chia, Anh T. N. Nguyen, Chengxue Qin, Rebecca H. Ritchie, Dana S. Hutchinson, Andrew Kompa, Paul J. White, Lauren T. May
Summary: Heart failure remains a significant cause of morbidity and mortality worldwide. Current treatment options have limitations, leading to many patients progressing to advanced stages. Exploration of novel therapeutics targeting G protein-coupled receptors (GPCRs) has shown promise, but efficacy and unwanted effects remain as challenges.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Pharmacology & Pharmacy
Mydirah Littlepage-Saunders, Michael J. Hochstein, Doris S. Chang, Kari A. Johnson
Summary: Dopamine transmission in the striatum is regulated by various G protein-coupled receptors (GPCRs) that bind neuromodulators, including dopamine itself. These GPCRs can modulate dopamine release by acting on different components of the dopaminergic circuitry and can have distinct effects on behavior and psychoactive drug actions. This review discusses the mechanisms by which GPCRs regulate dopaminergic transmission and their relevance to the effects of psychoactive drugs on physiology and behavior.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jing Chen, Xin Cai, Maocai Yan, Zhengwen Wang, Zhitong Lv, Chunmei Wang
Summary: By combining experimental and calculation approaches, the study successfully identified and characterized the interfaces of GPCR receptor dimers, and constructed atomic resolution models.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
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
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
Biochemistry & Molecular Biology
John Simms, Romez Uddin, Thomas P. Sakmar, Joseph J. Gingell, Michael L. Garelja, Debbie L. Hay, Margret A. Brimble, Paul W. Harris, Christopher A. Reynolds, David R. Poyner
Article
Immunology
Duncan I. Mackie, Fuad Al Mutairi, Reema B. Davis, Daniel O. Kechele, Natalie R. Nielsen, Joshua C. Snyder, Marc G. Caron, Harvey J. Kliman, Jonathan S. Berg, John Simms, David R. Poyner, Kathleen M. Caron
JOURNAL OF EXPERIMENTAL MEDICINE
(2018)
Article
Biochemistry & Molecular Biology
Sian Bailey, Matthew Harris, Kerry Barkan, Ian Winfield, Matthew Thomas Harper, John Simms, Graham Ladds, Mark Wheatley, David Poyner
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2019)
Article
Biochemistry & Molecular Biology
Sarah J. Routledge, John Simms, Ashley Clark, Ho Yan Yeung, Mark J. Wigglesworth, Ian M. Dickerson, Philip Kitchen, Graham Ladds, David R. Poyner
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Biochemistry & Molecular Biology
Sang-Min Lee, Yejin Jeong, John Simms, Margaret L. Warner, David R. Poyner, Ka Young Chung, Augen A. Pioszak
JOURNAL OF MOLECULAR BIOLOGY
(2020)
Review
Biochemical Research Methods
Daniel N. Wiseman, Abigail Otchere, Jaimin H. Patel, Romez Uddin, Naomi L. Pollock, Sarah J. Routledge, Alice J. Rothnie, Cathy Slack, David R. Poyner, Roslyn M. Bill, Alan D. Goddard
PROTEIN EXPRESSION AND PURIFICATION
(2020)
Article
Polymer Science
Jonathan A. Bollinger, Mark J. Stevens, Amalie L. Frischknecht
Article
Biochemistry & Molecular Biology
Aiman A. Gulamhussein, Romez Uddin, Brian J. Tighe, David R. Poyner, Alice J. Rothnie
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Biology
Ashley J. Clark, Niamh Mullooly, Dewi Safitri, Matthew Harris, Tessa de Vries, Antoinette MaassenVanDenBrink, David R. Poyner, Davide Gianni, Mark Wigglesworth, Graham Ladds
Summary: Agonist bias refers to different ligands producing distinct signaling outputs at the same receptor, with physiological consequences demonstrated for the CLR receptor. This study reveals that GPCR agonist bias occurs naturally in human cells and plays a fundamental role in providing unique functions to endogenous agonists, opening up possibilities for further research on RAMP function in native environments.
COMMUNICATIONS BIOLOGY
(2021)
Article
Endocrinology & Metabolism
Ian Winfield, Kerry Barkan, Sarah Routledge, Nathan J. Robertson, Matthew Harris, Ali Jazayeri, John Simms, Christopher A. Reynolds, David R. Poyner, Graham Ladds
Summary: This study investigates the role of the first intracellular loop (ICL1) and the eighth helix (H8) in signal transduction pathways of G protein-coupled receptors (GPCRs). The results suggest that mutations in ICL1 can affect cAMP production and Ca-i(2+) elevation, while having little impact on ERK1/2 activation. Additionally, an insertion in ICL1 is found to switch signaling bias between Ca-i(2+) and cAMP. Molecular dynamics simulations indicate that changes in ICL1 alter the conformation of ICL2 and the H8/TM7 junction.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Multidisciplinary Sciences
Clare. R. Harwood, David A. Sykes, Bradley L. Hoare, Franziska M. Heydenreich, Romez Uddin, David R. Poyner, Stephen J. Briddon, D. B. Veprintsev
Summary: The study demonstrated the isolation of beta 2-adrenoceptor (beta 2AR) using a polymer, diisobutylene maleic acid (DIBMA), which showed improved functional and thermal stability compared to traditional detergent methods. This unique method offers significant advantages for biophysical studies of beta 2AR.
Article
Chemistry, Multidisciplinary
Rachael L. Grime, Richard T. Logan, Stephanie A. Nestorow, Pooja Sridhar, Patricia C. Edwards, Christopher G. Tate, Bert Klumperman, Tim R. Dafforn, David R. Poyner, Philip J. Reeves, Mark Wheatley
Summary: Membrane proteins encapsulated in various polymer-based nano-encapsulation strategies exhibit different conformational changes, leading to the generation of diverse intermediate states for the proteins, which can be useful for studying membrane proteins effectively.
Article
Biochemistry & Molecular Biology
Sarah J. Routledge, Mohammed Jamshad, Haydn A. Little, Yu-Pin Lin, John Simms, Alpesh Thakker, Corinne M. Spickett, Roslyn M. Bill, Tim R. Dafforn, David R. Poyner, Mark Wheatley
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2020)
Article
Chemistry, Multidisciplinary
Rachael L. Grime, Joelle Goulding, Romez Uddin, Leigh A. Stoddart, Stephen J. Hill, David R. Poyner, Stephen J. Briddon, Mark Wheatley
Review
Pharmacology & Pharmacy
Debbie L. Hay, Michael L. Garelja, David R. Poyner, Christopher S. Walker
BRITISH JOURNAL OF PHARMACOLOGY
(2018)
Article
Biochemistry & Molecular Biology
G. F. Senguel, R. Mishra, E. Candiello, P. Schu
Summary: AP2 forms AP2 CCV with clathrin and other coat proteins, and synapses contain different types of CCV. The stability and composition of CCV are regulated by various factors, including Hsc70 and phosphorylation patterns. The knockout of the AP1/O1B complex disrupts synaptic vesicle recycling and endosomal protein sorting, leading to upregulation of endocytosis. Stable CCV, termed stCCV, have distinct characteristics and specialized functions in synaptic plasticity. The phosphorylation of Hsc70 and the levels of kinases play a crucial role in regulating the stability and disassembly of clathrin in CCV.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Martin Fluck, Colline Sanchez, Vincent Jacquemond, Christine Berthier, Marie-Noelle Giraud, Daniel Jacko, Kathe Bersiner, Sebastian Gehlert, Guus Baan, Richard T. Jaspers
Summary: Enhancing CaMKII signaling improves fatigue resistance and contractile characteristics of skeletal muscle by enhancing calcium release.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Letter
Biochemistry & Molecular Biology
Federica Coppola, Sara Monaci, Alessandro Falsini, Carlo Aldinucci, Irene Filippi, Daniela Rossi, Fabio Carraro, Antonella Naldini
Summary: The adaptor protein p62 plays a crucial role in maintaining the survival of dendritic cells (DCs) under hypoxic conditions by preserving Erk1/2 phosphorylation and reducing AMPK activation, thus extending their lifespan to ensure their functions in hypoxic microenvironments.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Jenifer Pendiuk Goncalves, Jorvani Cruz Villarreal, Sierra A. Walker, Xuan Ning Sharon Tan, Chad Borges, Joy Wolfram
Summary: This study used a mass spectrometry-based approach to assess the differences in glycan features between extracellular vesicles (EVs) and originating cells. The results showed that EVs selectively enriched specific glycan features, particularly those associated with binding to the extracellular matrix. The study also found differences in EV glycan sorting between different metastatic cell lines and mouse models, indicating a potential role of glycan diversity in the metastatic process.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
De-ao Gong, Peng Zhou, Wen-yi Chang, Jia-yao Yang, Yan-lai Zhang, Ai-long Huang, Ni Tang, Kai Wang
Summary: Liver cancer, ranked sixth globally, is a major contributor to cancer-related mortality. Metastasis is the main cause of treatment failure and deaths in liver cancer. The SPOP-CREB5-MET axis plays a significant role in liver cancer metastasis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Ning Huang, Jun Tang, Xiaoyao Yi, Maoxin Zhang, Bin Li, Yuan Cheng, Jin Chen
Summary: This study reveals that glioma-derived S100A9 can induce microglial M2 polarization, inhibit CD8+ T lymphocytes, and promote immunosuppression. The mechanism is related to the interaction with alpha v133 integrin and subsequent activation of AKT1 in microglia. The expression of S100A9 is positively associated with CD206 expression and negatively correlated with CD8+ T lymphocyte accumulation in the TME, suggesting a potential role of S100A9 in regulating the tumor microenvironment and immune evasion in glioma.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Yomna S. Abd El-Aziz, Matthew J. McKay, Mark P. Molloy, Betty McDowell, Elizabeth Moon, Loretta Sioson, Amy Sheen, Angela Chou, Anthony J. Gill, Patric J. Jansson, Sumit Sahni
Summary: This study identified a novel combination of autophagy inhibitors that can effectively inhibit the proliferation of oral squamous cell carcinoma (OSCC) cells, including both chemosensitive and chemoresistant cells. This research is important for the development of new therapies for advanced OSCC tumors.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Luojia Liu, Xiaoqiang Liu, Ying Chen, Meng Kong, Jinghong Zhang, Min Jiang, Hongling Zhou, Jinrui Yang, Xu Chen, Ze Zhang, Chao Wu, Xupin Jiang, Jiaping Zhang
Summary: Our study revealed that the Paxillin/HDAC6 signaling pathway regulates microtubule acetylation in electric field-guided keratinocyte migration.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Julia Weikum, Jeroen F. van Dyck, Saranya Subramani, David P. Klebl, Merete Storflor, Stephen P. Muench, Soren Abel, Frank Sobott, J. Preben Morth
Summary: The study reveals the complex interaction between bacterial magnesium transporter A (MgtA) and cardiolipin 18:1 and cardiolipin 16:0, highlighting the importance of lipid environment in protein activity and stability. Further understanding of Mg2+ homeostasis in bacteria will provide insights into bacterial infections.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Sumit Kinger, Yuvraj Anandrao Jagtap, Ankur Rakesh Dubey, Prashant Kumar, Akash Choudhary, Rohan Dhiman, Vijay Kumar Prajapati, Deepak Chitkara, Krishna Mohan Poluri, Amit Mishra
Summary: Efficient protein synthesis and quality control mechanisms are crucial for maintaining proteostasis and preventing neurodegeneration. This study demonstrates that treating cells with Lanosterol can enhance the proteolytic activity of Proteasome and promote the removal of misfolded proteins, suggesting a potential therapeutic approach for abnormal protein accumulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Karolina Stepien, Adrianna Skoneczna, Monika Kula-Maximenko, Lukasz Jurczyk, Mateusz Molon
Summary: The replication of DNA requires a complex machinery called the replisome, which is highly conserved across species. One crucial component of the replisome is the CMG helicase complex, which unwinds DNA and coordinates the assembly and function of other replisome components. In this study, the impact of the absence of one copy of the CMG complex genes on the physiology and aging of yeast cells was investigated. The findings showed disruptions in the cell cycle, extended doubling times, and alterations in the biochemical profile of these cells. Importantly, it was found that heterozygous cells for CMG helicase genes exhibited increased reproductive potential and delayed aging. The study also highlighted potential therapeutic targets for cancer treatment using yeast.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Nishadh Rathod, Guadalupe Guerrero-Serna, Howard S. Young, L. Michel Espinoza-Fonseca
Summary: This study reveals that replacing Lys27 with Asn enhances the inhibitory potency of MLN without affecting SERCA's affinity for Ca2+. The findings suggest that the SERCA site modulating Ca2+ affinity also functions as a catalytic activity switch.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Can Jiang, Chunyang Zhang, Min Dai, Fuyan Wang, Sa Xu, Dan Han, Yanyan Wang, Yajie Cao, Yanyan Liang, Ziyu Zhang, Lina Yan, Yujun Shen, Kewu He, Yuxian Shen, Jun Liu
Summary: The phosphorylation of p65 and the expression of SUMO1 are increased in cancer tissues of HCC patients, and there is a positive correlation between SUMO1 and phosphorylated p65. SUMOylation of p65 by SUMO1 promotes p65 nuclear import and enhances NF-xB activity. Both SUMOylation and phosphorylation of p65 increase the viability and invasion of hepatoma cells, and decrease cell apoptosis.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Ming-Fo Hsu, Yoshihiro Ito, Jai Prakash Singh, Shu-Fang Hsu, Alan Wells, Kuang-Yu Jen, Tzu-Ching Meng, Fawaz G. Haj
Summary: This study identified alpha-actinin4 as a novel substrate of PTP1B in podocytes and demonstrated their interaction in regulating podocyte function. Targeting PTP1B and alpha-actinin4 could be a potential therapeutic approach for podocyte injury.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)
Article
Biochemistry & Molecular Biology
Paulo F. V. Bizerra, Eduardo H. Gilglioni, Hang Lam Li, Simei Go, Ronald P. J. Oude Elferink, Arthur J. Verhoeven, Jung -Chin Chang
Summary: This study investigates the role of cyclic AMP (cAMP) in glycogen metabolism and reveals that cAMP regulates glycogenolysis in opposite directions depending on its site of synthesis within cells and downstream effectors. The canonical tmAC-cAMP-PKA signaling promotes glycogenolysis, while the non-canonical sAC-cAMP-Epac1 signaling suppresses glycogenolysis. This highlights the importance of cAMP microdomain organization for distinct metabolic regulation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2024)