Article
Biochemistry & Molecular Biology
Lukas Gratz, Tonis Laasfeld, Anni Allikalt, Corinna G. Gruber, Andrea Pegoli, Maris-Johanna Tahk, Mari-Liis Tsernant, Max Keller, Ago Rinken
Summary: This study compared BRET and FA fluorescence techniques in the characterization of ligand binding to GPCRs, using M2R and TAMRA-labeled ligands as a model system. The results showed that both methods yielded consistent affinities with radioligand competition binding experiments and provided real-time kinetic binding data. Additionally, the study demonstrated that BRET and FA assays can serve as valuable alternatives to radioactivity-based methods for screening purposes and for a precise characterization of binding kinetics.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Vlad Radoi, Gerd Jakobsson, Vinko Palada, Andrej Nikosjkov, Henrik Druid, Lars Terenius, Eva Kosek, Vladana Vukojevic
Summary: The dynamic interplay between the opioid and serotonin neuromodulatory systems plays an important role in chronic pain. This study investigates the integration of these systems at the single-cell level through direct interactions between mu-opioid and serotonin 1A receptors. The results suggest that the prolonged exposure to certain non-peptide opioids can facilitate heterodimerization of these receptors and stabilize the heterodimer complexes. Additionally, the study explores the different effects of non-peptide opioids on intracellular signaling pathways and calcium levels.
Article
Biochemistry & Molecular Biology
Parijat Sarkar, Amitabha Chattopadhyay
Summary: This Perspective discusses the emerging feature of closely bound cholesterol molecules in high-resolution GPCR structures and shares recent advancements in the field. The laboratory's journey in elucidating the functional sensitivity of GPCRs to membrane cholesterol, particularly using the serotonin(1A) receptor, is highlighted. A critical analysis of caveats involved in GPCR structure determination is also provided.
CHEMISTRY AND PHYSICS OF LIPIDS
(2021)
Article
Multidisciplinary Sciences
Minfei Su, Jinan Wang, Guoqing Xiang, Hung Nguyen Do, Joshua Levitz, Yinglong Miao, Xin-Yun Huang
Summary: α(1)-adrenergic receptors (α(1)-ARs) are crucial in regulating blood pressure, cognition, and metabolism. The lack of specific agonists for all subtypes of α(1)-ARs has hindered our understanding of their physiological roles and drug development. This study reveals the molecular mechanisms underlying the discrimination between α(1A)-AR and α(1B)-AR by the agonist A61603, providing insights for the rational design of subtype-specific agonists.
NATURE COMMUNICATIONS
(2023)
Article
Psychiatry
Hanga Galfalvy, Eileen Shea, Jacqueline de Vegvar, Spiro Pantazatos, Yung-yu Huang, Ainsley K. Burke, M. Elizabeth Sublette, Maria A. Oquendo, Francesca Zanderigo, Jeffrey M. Miller, J. John Mann
Summary: Childhood and lifetime adversity may influence brain serotonergic neurotransmission through epigenetic mechanisms. This study found that recent stress was correlated with DNA methylation of the 5-HT1A receptor gene and binding potential in participants with major depressive disorder (MDD), but not in controls. Childhood adversity was not associated with methylation or binding potential in MDD participants.
BRITISH JOURNAL OF PSYCHIATRY
(2023)
Article
Biology
Giovanna Di Nardo, Almerinda Di Venere, Chao Zhang, Eleonora Nicolai, Silvia Castrignano, Luisa Di Paola, Gianfranco Gilardi, Giampiero Mei
Summary: The study investigates the impact of two single-nucleotide polymorphisms on the dynamics of the aromatase protein, finding that mutations alter protein flexibility, affecting substrate binding and catalytic activity. The findings suggest a structural change in the variants and highlight a possible target for aromatase inhibition in helix G.
Article
Multidisciplinary Sciences
Clemens Schulte, Vladimir Khayenko, Noah Frieder Nordblom, Franziska Tippel, Violetta Peck, Amit Jean Gupta, Hans Michael Maric
Summary: Protein-protein interactions are crucial for understanding physiology and pathology, with short linear motifs playing a key role. Current approaches for determining protein-peptide affinity have limitations, but the TRIC method presents a high-throughput way to analyze these interactions in solution. TRIC allows for the identification and mapping of protein interaction sites with varying affinities, providing a label-free method for determining binding affinities of unmodified peptide libraries.
Review
Biochemistry & Molecular Biology
Shuai Hu, Kaiming Yu, Jianbin Yan, Xiaoyi Shan, Daoxin Xie
Summary: Phytohormones play a crucial role in integrating external and internal signals for plant survival and reproduction. Jasmonate (JA), an essential phytohormone, regulates diverse developmental processes and defense responses against environmental stresses. This review provides an overview of ligand-receptor binding techniques, the identification of the COI1 receptor and active JA molecules, and recent advances in JA perception and evolution.
Article
Biochemistry & Molecular Biology
Kenneth Dahl, Peter Johnstrom, Anton Forsberg-Moren, Bjorn Gustafsson, Patricia Miranda-Azpiazu, Yaser Khani, Christer Halldin, Lars Farde, Charles S. Elmore, Magnus Schou
Summary: This study reports the preparation and evaluation of two candidate 5-HT1A radioligands in vitro and in vivo. Although one of the radioligands showed high specific binding in human brain tissue, its regional binding potential values in cynomolgus monkey brain were low, suggesting it is not suitable for further investigation.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Katherine M. Stefanski, Charles M. Russell, Justin M. Westerfield, Rajan Lamichhane, Francisco N. Barrera
Summary: The impact of EphA2 receptor on cancer malignancy is determined by two different activation methods. PIP2 signaling lipid promotes TM dimerization in a conformation resembling the ligand-independent state, potentially affecting EphA2 activation. The difference in TM crossing angles in the ligand-dependent and ligand-independent states may play a role in regulating EphA2 activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Psychiatry
Elizabeth A. A. Bartlett, Ashley A. A. Yttredahl, Maura Boldrini, Andrea E. E. Tyrer, Kathryn R. R. Hill, Mala R. R. Ananth, Matthew S. S. Milak, Maria A. A. Oquendo, J. John Mann, Christine DeLorenzo, Ramin V. V. Parsey
Summary: This study found that childhood adversity is associated with the development and severity of depression in adulthood. However, the elevated serotonin 1A receptor (5-HT1AR) binding potential, which has been linked to major depression, was not replicated in this study. The findings suggest that childhood adversity may induce long-lasting changes in the expression of 5-HT1AR. The elevated hippocampal 5-HT1AR binding potential may serve as a promising biomarker to investigate the neurobiological link between childhood adversity and depression.
EUROPEAN PSYCHIATRY
(2023)
Article
Biology
Remy A. Yovanno, Tsung Han Chou, Sarah J. Brantley, Hiro Furukawa, Albert Y. Lau
Summary: This study investigated the mechanisms of D-serine in receptor activation and found that D-serine competes with glutamate for binding to GluN2A. The inhibitory effect of D-serine at high concentrations was confirmed through electrophysiology experiments.
Article
Cell Biology
Pengxiang Huang, Bradley M. Wierbowski, Tengfei Lian, Charlene Chan, Sara Garcia-Linares, Jiansen Jiang, Adrian Salic
Summary: This study reveals a unique role for GAS1 in catalyzing the assembly of the SHH-PTCH1 complex by transferring SHH from the extracellular carrier SCUBE2 to PTCH1 in vertebrate cells. Structure-guided experiments elucidate the mechanism of SHH movement and PTCH1 internalization, providing insights into morphogen reception and regulation.
DEVELOPMENTAL CELL
(2022)
Article
Chemistry, Medicinal
Yuko Tsuchiya, Tomoki Yonezawa, Yu Yamamori, Hiroko Inoura, Masanori Osawa, Kazuyoshi Ikeda, Kentaro Tomii
Summary: This article introduces the PoSSuM database, which can be used to identify similar binding pockets in proteins, and its drug search feature can investigate the diversity of ligands and receptors in these pockets. In addition, two new databases are introduced: PoSSuMAg for studying antibody-antigen interactions, and PoSSuMAF for simplifying the exploration of putative pockets in AlphaFold human protein models.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Biochemistry & Molecular Biology
Sarah El Kharraz, Vanessa Dubois, Martin E. van Royen, Adriaan B. Houtsmuller, Ekatarina Pavlova, Nina Atanassova, Tien Nguyen, Arnout Voet, Roy Eerlings, Florian Handle, Stefan Prekovic, Elien Smeets, Lisa Moris, Wout Devlies, Claes Ohlsson, Matti Poutanen, Kevin J. Verstrepen, Geert Carmeliet, Kaisa-Mari Launonen, Laura Helminen, Jorma J. Palvimo, Claude Libert, Dirk Vanderschueren, Christine Helsen, Frank Claessens
Summary: Dimerization of the ligand-binding domain of the androgen receptor (AR) is crucial for transcriptional regulation and proper functioning of AR. Mutations disrupting LBD dimerization can lead to significant effects, as demonstrated in a mouse model in this study.
Article
Biochemistry & Molecular Biology
Philipp Grad, Katarina Edwards, Lars Gedda, Victor Agmo Hernandez
Summary: This study investigates the effects of polyethylene glycol-(PEG) modified lipids and gangliosides on the Ca2+ induced interaction between liposomes composed of palmitoyl-oleoyl phosphatidylethanolamine (POPE) and palmitoyl-oleoyl phosphatidylserine (POPS) at physiological ionic strength. The results show that naked liposomes tend to adhere, rupture, and collapse on each other's surfaces upon addition of Ca2+, eventually resulting in the formation of large multilamellar aggregates and bilayer sheets. However, the presence of gangliosides or PEGylated lipids leads to the formation of small, long-lived bilayer fragments/disks. PEGylated lipids seem to be more effective than gangliosides at stabilizing these structures. The study suggests that direct liposome-liposome fusion is not the dominating process triggered by Ca2+ in the systems studied.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Saurabh Saraswat, Archana Chugh
Summary: Cell penetrating peptides (CPP) are important tools for intracellular delivery of molecules. In this study, a novel marine-derived CPP from Engraulis japonicus, called Engraulisin, was reported. Engraulisin demonstrated successful cellular uptake and selective antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA), making it a potential candidate for drug delivery.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Emanuela Efodili, Ashlynn Knight, Maryem Mirza, Cedric Briones, Il-Hyung Lee
Summary: This study demonstrates the spontaneous transfer of small membrane-bound peptides between a supported lipid bilayer and giant unilamellar vesicles in vitro. The transfer occurs through the formation of hemi-fusion stalks and is limited to small peptides due to the highly curved structure of the stalk. This system provides a synthetic platform for studying peptide trafficking between synthetic membranes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Yueqi Niu, Si Jia Chen, Jeffery B. Klauda
Summary: Macrophage membranes in the activated state are more tightly packed, exhibit increased chain order across lipid species, and form specific lipid clusters. These findings provide physiologically accurate models for future computational studies of macrophage membranes and their proteins.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Niki Baccile, Vincent Chaleix, Ingo Hoffmann
Summary: This study measured the bending rigidity of self-assembled structures formed by a new biobased glucolipid bioamphiphile using neutron spin-echo (NSE) technology. The results showed that the bending rigidity of these structures is lower or higher compared to phospholipid membranes, providing a new theoretical basis for the application of these new molecular systems.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Alain Bolano Alvares, Pablo E. A. Rodriguez, Gerardo D. Fidelio
Summary: The behavior of amphiphilic molecules at the air/water interface was studied to evaluate the arrangement formed in a confined area. The surface properties of zwitterionic DPPC lipid and A beta(1-40) amyloid peptide in mixed films were investigated at different temperatures. DPPC undergoes a phase transition depending on temperature and lateral pressure, which allows for the study of its influence on amyloid structure formation.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Lukasz Plachta, Marzena Mach, Magdalena Kowalska, Pawel Wydro
Summary: Resveratrol, a popular phytoalexin found in grapes and red wine, has beneficial effects on the cardiovascular system, exhibits antiviral, antibacterial, and antifungal properties, and may have therapeutic effects against cancer. This study investigates the interaction of resveratrol with model cell membranes, demonstrating changes in their physicochemical parameters and highlighting the role of cholesterol content in resveratrol incorporation. The findings suggest that the molecular mechanism of action of resveratrol may involve interactions with lipid rafts.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Edurne Rujas, Beatriz Apellaniz, Johana Torralba, David Andreu, Jose M. M. Caaveiro, Shixia Wang, Shan Lu, Jose L. Nieva
Summary: This study investigates the role of fusion peptide and Trp-rich membrane proximal external region in HIV-1 fusion and demonstrates that liposome-based formulations containing FP-MPER hybrid peptides can induce the production of specific neutralizing antibodies in rabbits. The results support the use of liposomes as vaccine carriers and the inclusion of lipid membranes in immunogens to elicit specific humoral responses.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Dailin Li, Dingyuan Shi, Lei Wang
Summary: G protein-gated inwardly rectifying potassium (GIRK) channels play a significant role in regulating cell excitability. This study investigated the ion permeation mechanism in GIRK2 mutants using molecular dynamic simulations and QM/MM methods. The results revealed the importance of a multi-ion distribution for ion conduction.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Max J. den Uijl, Arnold J. M. Driessen
Summary: Membrane protein insertion into and translocation across the bacterial cytoplasmic membrane are essential processes facilitated by the Sec translocon. The phospholipid dependence of membrane protein insertion has remained mostly unknown. This study reveals that the insertion of the mannitol permease MtlA into the membrane depends on the presence of phosphatidylglycerol and is stimulated by phosphatidylethanolamine.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Patrick Allen, Adam C. Smith, Vernon Benedicto, Abbas Abdulhasan, Vasanthy Narayanaswami, Enrico Tapavicza
Summary: We explore the stability, size, and structure of nanodiscs formed by the N-terminal domain of apolipoprotein E3 and a variable number of 1,2-dimyristoyl-sn-glycero-3-phosphocholine molecules. Our simulations suggest that nanodiscs containing 240 to 420 DMPC molecules are stable. The antiparallel configuration shows more protein-protein interactions and ionic contacts, as well as greater stability and rigidity compared to the parallel configuration.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Patrick M. Keating, Nicholas P. Schifano, Xinrui Wei, Matthew Y. Kong, Jinwoo Lee
Summary: Lassa virus (LASV) infection is dependent on the fusion of its viral membrane with the host cell membrane, and our study reveals that this fusion process involves pH-dependent conformational changes in the transmembrane domain of LASV. These findings provide valuable insights into the fusion mechanism of LASV and can be utilized in the design of therapeutics to combat Lassa virus infections and prevent its potential spread.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Ashley L. Bennett, Kristen N. Cranford, Austin L. Bates, Christopher R. Sabatini, Hee-Seung Lee
Summary: This study employed molecular dynamics simulations to elucidate the binding, folding, and insertion details of TP10W in the cell membrane. The simulations revealed that TP10W can translocate across the lipid membrane as a monomer, and the charged amino acid side chains can move between lipid leaflets. Comparison with point mutated variants demonstrated significant conformational changes due to charge distribution.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Article
Biochemistry & Molecular Biology
Jessica H. van Wonderen, Jason C. Crack, Marcus J. Edwards, Thomas A. Clarke, Gerhard Saalbach, Carlo Martins, Julea N. Butt
Summary: Electrogenic bacteria transfer excess respiratory electrons to metal oxide particles and electrodes through the MtrCAB complex. The crystal structure of MtrCAB from S. baltica OS185 was resolved, and liquid chromatography mass spectrometry was used to determine the mass values of the three proteins in purified MtrCAB complexes.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)
Review
Biochemistry & Molecular Biology
Yi-Ming Chen, Ching-Tai Lu, Chia-Wen Wang, Wolfgang B. Fischer
Summary: A series of dye ligands were ranked based on docking experiments, selecting the most suitable ligands for binding with different proteins. Additionally, a comparison study was conducted on a series of repurposing drugs and known antivirals.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2024)