Article
Pharmacology & Pharmacy
Harmandeep Kaur, Veera Ganesh Yerra, Sri Nagarjun Batchu, Duc Tin Tran, M. D. Golam Kabir, Youan Liu, Suzanne L. Advani, Phelopater Sedrak, Laurette Geldenhuys, Karthik K. Tennankore, Penelope Poyah, Ferhan S. Siddiqi, Andrew Advani
Summary: In this study, a transcriptional profile of activated kidney fibroblasts and the GPCRs they express was established in mouse models of kidney disease. The marker Tcf21 and the GPCRs Adgra2 and S1pr3 were found to be highly expressed in these activated fibroblasts. This research provides new insights into potential therapeutic targets for treating CKD.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Steven Lavington, Anthony Watts
Summary: The study investigates the use of PMA for detergent-free purification, showing potential advantages over SMA and compatibility with standard purification protocols. PMA-solubilised NTSR1 demonstrates better activation of heterotrimers compared to detergent-solubilised receptor.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Review
Chemistry, Medicinal
Hyeonyeong Im, Ji-Hyun Park, Seowoo Im, Juhyeong Han, Kyungmin Kim, Yun-Hee Lee
Summary: The high incidence of obesity has led to an increased need to discover new therapeutic targets. Recent research has shown that G-protein coupled receptors (GPCRs) could be potential therapeutic targets to regulate adipose tissue metabolism.
ARCHIVES OF PHARMACAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Yann Waltenspuhl, Jeliazko R. Jeliazkov, Lutz Kummer, Andreas Pluckthun
Summary: This study presents an engineering strategy to improve the properties of challenging GPCRs by combining three directed evolution methods. Utilizing a Next-Generation Sequencing (NGS) strategy, the study successfully selected improved variants of the human oxytocin receptor and compared mutations in different hosts. This research provides insights into the evolutionary pressure on the same membrane protein in prokaryotes and eukaryotes and offers a general methodology for accurate analysis of point mutants during directed evolution.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Canyong Guo, Lingyun Yang, Zhijun Liu, Dongsheng Liu, Kurt Wuthrich
Summary: Eight hundred and twenty-six human G protein-coupled receptors (GPCRs) play a significant role in mediating the actions of hormones, neurotransmitters, and drugs. Studying the structure and dynamics of GPCRs in lipid bilayer environments is crucial for understanding their functionality and developing new drugs. This study incorporates the A(2A) adenosine receptor into lipid nanodiscs, providing a detergent-free environment for structural studies using NMR. The findings demonstrate the stability and mimicry of the lipid nanodisc and LMNG/CHS micelles in preserving the overall fold and local structure of the receptor.
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
Biochemistry & Molecular Biology
Jeremie Topin, Cedric Bouysset, Jody Pacalon, Yiseul Kim, Mee-Ra Rhyu, Sebastien Fiorucci, Jerome Golebiowski
Summary: Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs), with their experimental structure yet to be determined and key-residues controlling their function mostly unknown. Researchers designed an integrative approach to improve comparative modeling of TAS2Rs.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Efpraxia Tzortzini, Antonios Kolocouris
Summary: Most membrane lipids interact with GPCRs structures and modulate their function. PIP2 and cholesterol have an impact on the conformational equilibria of the A(2A) adenosine receptor.
Article
Neurosciences
Wenqi Fu, Luca Franchini, Cesare Orlandi
Summary: This study generated new GPRC5B polyclonal antibodies and investigated the expression levels of GPRC5B in different organs and brain regions. It was found that GPRC5B had high levels of glycosylation in the mouse brain and was expressed at the highest level in the olfactory bulb, hippocampus, cerebellum, and pons. GABAergic neurons showed higher expression levels of Gprc5b than glutamatergic neurons in most regions.
FRONTIERS IN NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Sergi Ferre, Francisco Ciruela, Carmen W. Dessauer, Javier Gonzalez-Maeso, Terence E. Hebert, Ralf Jockers, Diomedes E. Logothetis, Leonardo Pardo
Summary: The study proposes the concept of GPCR-effect assemblies (GEMMAs), which are pre-assembled before receptor activation and allow more efficient interactions between specific signaling components. This offers an alternative model to the conventional collision coupling model and explains the differential properties of GPCRs in different cellular environments.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Cell Biology
Margaret A. Mouat, Brendan P. Wilkins, Eileen Ding, Hemna Govindaraju, James L. J. Coleman, Robert M. Graham, Nigel Turner, Nicola J. Smith
Summary: The deletion of GPR37L1 does not significantly affect glucose handling, body weight, and fat mass in mice. However, Gpr37l1(-/-) mice show lower fat mass accumulation and higher ambulatory activity during night hours.
Article
Biochemistry & Molecular Biology
Yanan Tian, Chaohui Jiang, Yi Pan, Zhiqiang Guo, Weiwei Wang, Xumei Luo, Zheng Cao, Bing Zhang, Jingwen Yang, Ying Shi, Naiming Zhou, Xiaobai He
Summary: Two newly identified CCHamide receptors, BommoCCHaR-1 and -2, have been cloned and their specific endogenous ligands, CCHamide-1 and CCHamide-2, respectively, have been characterized. The receptors exhibit different signaling pathways upon activation, with BNGR-A14 eliciting increases in CRE-driven luciferase activity, intracellular Ca2+ mobilization, and ERK1/2 phosphorylation, while BNGR-A15 leads to intracellular accumulation of cAMP, Ca2+ mobilization, and ERK1/2 phosphorylation. Additionally, CCHamides are shown to require intrachain disulfide bonds for activation, and CCHamide-1 may regulate feeding behavior and growth through BNGR-A15, while CCHamide-2 plays a crucial role in multiple physiological processes.
INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2021)
Review
Physiology
Davide Calebiro, Zsombor Koszegi, Yann Lanoiselee, Tamara Miljus, Shannon O'Brien
Summary: Recent research has revealed transient interactions between GPCRs and G proteins in living cells, resulting in short-lived signaling nanodomains that may confer rapidity and specificity to signal transduction. These findings could potentially offer new strategies for modulating GPCR function and pave the way for innovative drug development for common diseases like diabetes or heart failure.
PHYSIOLOGICAL REVIEWS
(2021)
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
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
Clinical Neurology
Mootaz M. Salman, Philip Kitchen, Andrea Halsey, Marie Xun Wang, Susanna Tornroth-Horsefield, Alex C. Conner, Jerome Badaut, Jeffrey J. Iliff, Roslyn M. Bill
Summary: AQP4 plays a crucial role in the central nervous system, regulating water exchange, cell volume, and astrocyte migration, and is associated with glymphatic function and neurodegenerative diseases.
Article
Biochemistry & Molecular Biology
Hiroaki Ishida, Hans J. Vogel, Alex C. Conner, Philip Kitchen, Roslyn M. Bill, Justin A. MacDonald
Summary: This study assessed the CaM-binding properties of AQP4, finding two putative CaM-binding domains in the cytoplasmic regions. The N-terminal CBD of AQP4 interacted predominantly with the N-lobe of CaM, while the C-terminal AQP4 peptide interacted with both the C-and N-lobes of CaM. The data support a unique adapter protein binding mode for CaM with AQP4.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Review
Biochemistry & Molecular Biology
Kim Wagner, Lucas Unger, Mootaz M. Salman, Philip Kitchen, Roslyn M. Bill, Andrea J. Yool
Summary: This review highlights the key roles of aquaporins (AQPs) in fluid homeostasis, glandular secretions, signal transduction and sensation, barrier function, immunity and inflammation, cell migration, and angiogenesis. It emphasizes that the functions of AQPs are more complex than simply mediating the flow of water. Further research and development of AQP inhibitors will provide new insights and treatments for AQP-associated disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Benjamin O. Ezema, Kingsley O. Omeje, Roslyn M. Bill, Alan D. Goddard, Sabinus Oscar O. Eze, Alfred Fernandez-Castane
Summary: Lipolytic fungus Aspergillus flavus was isolated, and its lipase gene was sequenced and characterized. The study revealed the presence of a lipase consensus sequence and a catalytic active site lid domain in the Aspergillus flavus lipase sequence. Furthermore, the study provided insights into the structural and molecular properties of the lipase, which will be crucial for future biotechnology applications.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Marine & Freshwater Biology
Margot K. Vermeylen, Toby G. Knowles, Heather W. Barron
Summary: The study reveals an increasing trend of Karenia brevis red tides along Florida's coast, potentially caused by anthropogenic eutrophication, which results in an increased number of affected wildlife. Moreover, water discharges from the Okeechobee waterway are significantly correlated with K. brevis densities. Different species groups exhibit significant correlations with K. brevis cell counts, particularly the double-crested cormorants.
Review
Agriculture, Dairy & Animal Science
K. A. Fletcher, G. Limon, L. J. Whatford, A. Grist, T. G. Knowles, T. J. Gibson
Summary: This systematic review found a lack of consistent guidance on equine slaughter globally, along with a shortage of research on equine welfare during the slaughter process, particularly concerning donkeys and mules in low-income countries. The need to urgently develop an evidence base to improve guidance in this area was highlighted.
Article
Biology
Maryam Jama, Marawan Ahmed, Anna Jutla, Carson Wiethan, Jitendra Kumar, Tae Chul Moon, Frederick West, Michael Overduin, Khaled H. Barakat
Summary: This study utilized computational tools to screen over 6 million compounds and identified three potent allosteric inhibitors of SHP2. The binding affinities of these inhibitors to SHP2 were measured and found to be in the nanomolar range, suggesting their potential as improved allosteric inhibitors of SHP2.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Virology
Michael Overduin, Rakesh K. K. Bhat, Troy A. A. Kervin
Summary: Variants of the Omicron subvariants of SARS-CoV-2 exhibit strong membrane binding abilities and can evade antibodies from vaccinations and previous infections. Despite differences around mutated sites, they all maintain elevated membrane binding propensities and exhibit both closed and open states. These findings provide predictive criteria for future pandemic waves and strategies for combating multiple variants.
Article
Biotechnology & Applied Microbiology
Hung M. Nguyen, Loan Q. Le, Luca Sella, Luke M. Broadbent, Roslyn M. Bill, Van V. Vu
Summary: This study successfully expressed MoAA16 heterologously in Pichia pastoris and revealed its cellulose-active PMO properties. MoAA16 can break down cellulose through oxidation and enhance cellulase hydrolysis, resulting in the production of more monosaccharide products. These findings highlight the potential of MoAA16 for applications in biofuel production and chemical synthesis.
ELECTRONIC JOURNAL OF BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Andrea Markou, Philip Kitchen, Ahmed Aldabbagh, Mariaelena Repici, Mootaz M. Salman, Roslyn M. Bill, Zita Balklava
Summary: The AQP4 water channel plays a crucial role in brain swelling following insults like traumatic injury or stroke, with its trafficking mechanisms involving early and recycling endosomes as well as cytoskeleton dynamics. AQP4 constantly cycles between the cell surface and intracellular vesicles in mammalian cells, with internalisation being dynamin-dependent. Targeting Rab5, Rab11, and cytoskeleton dynamics could provide potential avenues for edema treatment.
JOURNAL OF NEUROCHEMISTRY
(2023)
Review
Biotechnology & Applied Microbiology
Antonio Carlesso, Raquel Delgado, Oriol Ruiz Isant, Owens Uwangue, Dylan Valli, Roslyn M. Bill, Kristina Hedfalk
Summary: This study emphasizes the importance of yeast as a production host for eukaryotic membrane proteins. Yeast remains a useful host for studying α-helical membrane proteins, with both homologous and heterologous production being common in different yeast hosts.
FEMS YEAST RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Anh Tran, Troy A. Kervin, Michael Overduin
Summary: This study investigates the mechanism of interaction between the spike protein of SARS-CoV-2 and host cell membranes. Multiple binding sites between the spike protein and membranes are identified, which play a role in viral fusion, entry, assembly, and egress processes, as well as ACE2 receptor recognition. Antibodies targeting the spike protein block the membrane docking process that precedes ACE2 recognition.
CURRENT RESEARCH IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemical Research Methods
Tamim Al-Jubair, Jonas Hyld Steffen, Julie Winkel Missel, Philip Kitchen, Mootaz M. Salman, Roslyn M. Bill, Pontus Gourdon, Susanna Tornroth-Horsefield
Summary: This article describes a protocol for characterizing the interaction between a human AQP and a soluble interaction partner using microscale thermophoresis (MST). The protocol provides a high level of control over components and environment, allowing for investigation of AQP protein-protein interactions with low sample consumption and high detergent compatibility.
Article
Biochemical Research Methods
Tamim Al-Jubair, Jonas Hyld Steffen, Julie Winkel Missel, Philip Kitchen, Mootaz M. Salman, Roslyn M. Bill, Pontus Gourdon, Susanna Tornroth-Horsefield
Summary: This article presents a protocol for high-yield recombinant expression and purification of human AQPs in the methylotropic yeast Pichia pastoris.
Article
Biochemical Research Methods
Jonas Hyld Steffen, Julie Winkel Missel, Tamim Al-Jubair, Philip Kitchen, Mootaz M. Salman, Roslyn M. Bill, Susanna Tornroth-Horsefield, Pontus Gourdon
Summary: AQPs, as critical water channels, play an important role in maintaining water homeostasis. This protocol describes a method to determine the water permeation capacity of AQPs by tracking the change in proteoliposome size exposed to an osmogenic gradient.