Article
Biochemistry & Molecular Biology
Evan van Aalst, Jotham Koneri, Benjamin J. Wylie
Summary: Investigations into cholesterol binding sites in CCR3 have revealed the presence of multiple binding sites containing Cholesterol Recognition/Interaction Amino Acid Consensus motif (CRAC) and its inversion CARC motifs, with a particular site in TM1 and TM7 emerging as a candidate for future research based on cholesterol residency time and conservation in other chemokine receptors. These cholesterol binding sites may provide insights into cholesterol regulation mechanisms in the subfamily of Class A GPCRs.
Review
Biochemistry & Molecular Biology
Diego Guidolin, Cinzia Tortorella, Manuela Marcoli, Chiara Cervetto, Guido Maura, Luigi F. Agnati
Summary: The discovery of allosteric receptor-receptor interactions and receptor complexes in intercellular communication has expanded our understanding of the nervous system. Research on neuronal populations and receptor complexes has led to insights on synaptic efficiency tuning, with potential implications for neuroprotective therapeutic strategies. More research is still needed in this area to fully explore the implications of receptor-receptor interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Salma Pathan-Chhatbar, Carina Drechsler, Kirsten Richter, Anna Morath, Wei Wu, Bo OuYang, Chenqi Xu, Wolfgang W. Schamel
Summary: Biological membranes are composed of a variety of lipids and proteins, with plasma membrane cholesterol playing a dual role in the activation of the αβ T cell receptor. Cholesterol binding to the TCR β subunit's TM domain maintains the TCR in an inactive state, while also increasing TCR clustering to enhance the sensitivity of the αβ T cell.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cardiac & Cardiovascular Systems
Laura M. Wingler, Andrew P. Feld
Summary: Understanding the activation of G protein-coupled receptors (GPCRs) is crucial in cardiovascular medicine. Nanobodies, recombinant single-domain antibody fragments, have become important tools to study GPCRs in purified systems and living cells. The use of nanobodies has revealed the characteristics of GPCRs in terms of their structure, pharmacology, and signaling, and has the potential to have a significant impact in both basic science and therapeutic applications.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2022)
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
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.
Article
Biochemistry & Molecular Biology
Jordan M. Mattheisen, Jaina S. Wollowitz, Thomas Huber, Thomas P. Sakmar
Summary: We developed a luciferase-based reporter assay for site-specific bioorthogonal labeling of expressed G protein-coupled receptors (GPCRs) in live cells. The assay compared amber codon suppression efficiency, receptor functionality, and efficiency of different bioorthogonal labeling chemistries. We used three different noncanonical amino acids to incorporate into a GPCR, resulting in successful labeling and functional assessment of the engineered mutants in live cells.
Article
Biochemistry & Molecular Biology
Simona Daniele, Simona Saporiti, Stefano Capaldi, Deborah Pietrobono, Lara Russo, Uliano Guerrini, Tommaso Laurenzi, Elham Ataie Kachoie, Luca Palazzolo, Vincenzo Russo, Maria Pia Abbracchio, Ivano Eberini, Maria Letizia Trincavelli
Summary: GPR17, a key regulator of myelination, is activated by endogenous ligands and pro-inflammatory molecules. This study investigates the structural and functional interactions between GPR17 and chemokine receptors CXCR2 and CXCR4. The results show that these receptors can form heterodimers and modulate intracellular cAMP levels. This cross-talk between receptors could impact the neuroinflammatory environment associated with demyelinating events.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Madhura Mohole, Durba Sengupta, Amitabha Chattopadhyay
Summary: The interaction between lipids and G-protein-coupled receptors (GPCRs) can modulate receptor organization and function. This study analyzes the lipid-lipid crosstalk at the serotonin1A receptor and identifies synergistic cobinding and competitive binding between different lipids.
ACS CHEMICAL NEUROSCIENCE
(2022)
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
Mengrong Li, Yiqiong Bao, Ran Xu, Honggui La, Jingjing Guo
Summary: This study used molecular dynamics simulations to investigate the binding of parathyroid hormone receptor to G-protein, as well as how calcium ions allosterically engage in the process. The results showed that calcium ions stabilize the conformation of the complex and promote interaction between the receptor and G-protein, revealing insights into possible allosteric signaling pathways.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Xianlong Gao, Matthias Majetschak
Summary: It is unclear whether the heteromerization of CXCR4, ACKR3, and alpha(1b)-AR affects the effects of CXCL12 and ubiquitin on G protein activation. Biophysical evidence shows that both ligands stimulate CXCR4-mediated Gai activation, but ubiquitin fails to recruit b-arrestin. Additionally, the ligands modulate the conformation of CXCR4:ACKR3 heterodimers and their interaction with alpha(1b)-AR.
Article
Biochemistry & Molecular Biology
Laura Lemel, Katarzyna Niescierowicz, M. Dolores Garcia-Fernandez, Leonardo Darre, Thierry Durroux, Marta Busnelli, Mylene Pezet, Fabrice Rebeille, Juliette Jouhet, Bernard Mouillac, Carmen Domene, Bice Chini, Vadim Cherezov, Christophe J. Moreau
Summary: The study revealed a stable binding of cholesterol molecules to OXTR in the presence of orthosteric ligands, leading to a positive cross-regulation between cholesterol and orthosteric ligands, which preserves the activity of the receptor in cholesterol-depleted membranes.
JOURNAL OF LIPID RESEARCH
(2021)
Article
Biology
Cristina Velasco, Marta Conde-Sieira, Sara Comesana, Mauro Chivite, Jesus M. Miguez, Jose L. Soengas
Summary: In this study using rainbow trout as a model, the G protein-coupled receptors GPR84 and GPR119 were investigated for their roles in food intake regulation. The treatment with agonists for these receptors induced an anorectic response in the fish, leading to changes in mRNA abundance of neuropeptides and related transcription factors. These changes were associated with phosphorylation status of FOXO1, AMPKa, and Akt, as well as signaling pathways related to PLC beta and IP3.
JOURNAL OF EXPERIMENTAL BIOLOGY
(2021)
Article
Pathology
Enrica Saponara, Carlos Penno, Vanessa Orsini, Zhong-Yi Wang, Audrey Fischer, Alexandra Aebi, Meztli L. Matadamas-Guzman, Virginie Brun, Benoit Fischer, Margaret Brousseau, Peter O'Donnell, Jonathan Turner, Alexandra Graff Meyer, Laura Bollepalli, Giovanni dArio, Guglielmo Roma, Walter Carbone, Stefano Annunziato, Michael Obrecht, Nicolau Beckmann, Chandra Saravanan, Arnaud Osmont, Philipp Tropberger, Shola M. Richards, Christel Genoud, Svenja Ley, Iwona Ksiazek, Florian Nigsch, Luigi M. Terracciano, Heiko S. Schadt, Tewis Bouwmeester, Jan S. Tchorz, Heinz Ruffner
Summary: This study investigated the role of Lgr4/5 in nonalcoholic fatty liver disease (NAFLD) and found that the loss of Lgr4/5 in hepatic epithelial cells led to hepatic steatosis and fibrosis in mice fed with a high-fat diet. The study also demonstrated that the loss of Lgr4/5 resulted in impaired bile acid secretion, altered lipid homeostasis, and deregulation of lipoprotein pathways, all of which contributed to the onset of NAFLD.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Chemistry, Physical
Apoorva Sridhar, Mustafizur Rahman, Antonia Infantes-Molina, Benjamin J. Wylie, Collin G. Borcik, Sheima J. Khatib
APPLIED CATALYSIS A-GENERAL
(2020)
Article
Multidisciplinary Sciences
Reza Amani, Collin G. Borcik, Nazmul H. Khan, Derek B. Versteeg, Maryam Yekefallah, Hoa Q. Do, Heather R. Coats, Benjamin J. Wylie
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Biochemistry & Molecular Biology
Evan Van Aalst, Maryam Yekefallah, Anil K. Mehta, Isaac Eason, Benjamin Wylie
Article
Chemistry, Multidisciplinary
Collin G. Borcik, Derek B. Versteeg, Reza Amani, Maryam Yekefallah, Nazmul H. Khan, Benjamin J. Wylie
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Multidisciplinary Sciences
Aveline Hewetson, Nazmul H. Khan, Matthew J. Dominguez, Hoa Quynh Do, R. E. Kusko, Collin G. Borcik, Daniel J. Rigden, Ronan M. Keegan, R. Bryan Sutton, Michael P. Latham, Benjamin J. Wylie, Gail A. Cornwall
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Nanoscience & Nanotechnology
Jiyun Hu, Federica Zanca, Gregory J. McManus, Isabella A. Riha, Huong Giang T. Nguyen, William Shirley, Collin G. Borcik, Benjamin J. Wylie, Mourad Benamara, Roger D. van Zee, Peyman Z. Moghadam, Hudson Beyzavi
Summary: Chemists have been continuously seeking new linkages for covalent organic frameworks (COFs) as they form the foundation for the materials' structure and properties. A novel strategy using H3PO3 as a bifunctional catalyst was reported to achieve amine-linked COFs from easily obtainable amine and aldehyde linkers. The amine-linked COF was found to outperform its imine analogue in promoting Knoevenagel condensation due to its more basic sites and higher stability.
ACS APPLIED MATERIALS & INTERFACES
(2021)
Article
Biochemistry & Molecular Biology
Evan van Aalst, Jotham Koneri, Benjamin J. Wylie
Summary: Investigations into cholesterol binding sites in CCR3 have revealed the presence of multiple binding sites containing Cholesterol Recognition/Interaction Amino Acid Consensus motif (CRAC) and its inversion CARC motifs, with a particular site in TM1 and TM7 emerging as a candidate for future research based on cholesterol residency time and conservation in other chemokine receptors. These cholesterol binding sites may provide insights into cholesterol regulation mechanisms in the subfamily of Class A GPCRs.
Article
Chemistry, Multidisciplinary
Collin G. Borcik, Isaac R. Eason, Maryam Yekefallah, Reza Amani, Ruixian Han, Boden H. Vanderloop, Benjamin J. Wylie
Summary: Cholesterol oligomers are found in various membrane protein crystal structures, but their biological function is not well understood. This study presents the structural and functional details of a cholesterol dimer that stabilizes the inactivated state of an inward-rectifier potassium channel. The findings provide insights into the role of cholesterol oligomers in regulating channel conductance.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Evan J. G. van Aalst, Collin J. Borcik, Benjamin Wylie
Summary: Membrane proteins and polycyclic lipids coordinate phospholipid bilayer ordering, resulting in the partitioning of liquid crystalline phase. This ordering plays important roles in signal transduction in eukaryotes and pathogenicity and antimicrobial resistance in prokaryotes. Experimental evidence indicates microdomain formation and lipid ordering in native membranes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Biochemistry & Molecular Biology
Reza Amani, Charles D. Schwieters, Collin G. Borcik, Isaac R. Eason, Ruixian Han, Benjamin D. Harding, Benjamin J. Wylie
Summary: Using solid-state NMR measurements of water proximity information and refining the membrane protein structure in simulations has proven to be an effective method for improving structural resolution.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Collin G. Borcik, Isaac R. Eason, Boden Vanderloop, Benjamin J. Wylie
Summary: This study presents a cost-effective method for the enrichment of cholesterol using H-2 and C-13 labeling. The labeling pattern of cholesterol is characterized and its utility in reporting cholesterol dynamics and orientation in various environments is demonstrated. The flexibility and universality of this labeling technique allow it to be widely applied to different lipid molecules and natural products.
Article
Chemistry, Multidisciplinary
Maryam Yekefallah, Carver A. Rasberry, Evan J. Van Aalst, Holley P. Browning, Reza Amani, Derek B. Versteeg, Benjamin J. Wylie
Summary: Potassium channels are regulated by allosteric communication between the helical bundle crossing and the selectivity filter. KirBac1.1 is a bacterial potassium channel that is gated by the anionic phospholipid ligand PG. Site-directed mutagenesis and molecular dynamics simulations were used to investigate the gating mechanism and allosteric network of KirBac1.1.
Article
Chemistry, Medicinal
Evan J. van Aalst, Corey J. McDonald, Benjamin J. Wylie
Summary: Cholesterol plays a role in directing the signal transduction pathway of ligand-induced G protein coupled receptors (GPCRs). We have discovered a correlation between cholesterol and increased CCR3 signal transduction. However, the molecular mechanism underlying this increase in affinity and coupling is still unknown.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Xiaodan Ding, Daniel K. K. Unruh, Liulei Ma, Evan J. J. van Aalst, Eric W. W. Reinheimer, Benjamin J. J. Wylie, Kristin M. M. Hutchins
Summary: We describe the colossal and anisotropic thermal expansion in crystals of an organic compound. At high temperature, the material exhibits two-dimensional zero area expansion and colossal positive linear expansion due to dynamic motion. At low temperature, moderate positive expansion occurs in all directions. Investigation of solid-state motion and cycling experiments confirm the reversibility of the expansion behavior. These results provide strategies for designing anisotropic and switchable behavior in solid-state materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)