A5015112336- Receptor Mechanisms and Signaling
- Connexins and lens biology
- Neuropeptides and Animal Physiology
- Nicotinic Acetylcholine Receptors Study
- Protein Kinase Regulation and GTPase Signaling
- Mass Spectrometry Techniques and Applications
- Ion channel regulation and function
- Yersinia bacterium, plague, ectoparasites research
- Monoclonal and Polyclonal Antibodies Research
- Forensic Entomology and Diptera Studies
- Neuroscience and Neuropharmacology Research
- Photoreceptor and optogenetics research
- Gas Sensing Nanomaterials and Sensors
- Insect behavior and control techniques
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Diptera species taxonomy and behavior
- RNA and protein synthesis mechanisms
- Integrated Circuits and Semiconductor Failure Analysis
- 2D Materials and Applications
- bioluminescence and chemiluminescence research
- Natural product bioactivities and synthesis
- Heat shock proteins research
- Ruminant Nutrition and Digestive Physiology
- Semiconductor materials and devices
University of Michigan
2025
Stanford University
2015-2023
Osaka University
1994-2021
Nissin Kogyo (Japan)
2021
Paul Scherrer Institute
2011-2019
ETH Zurich
2014
Semiconductor Energy Laboratory (Japan)
2014
University of Hyogo
2010-2011
Protein Research Foundation
2009-2010
Kyoto University
2002-2003
Choosing a partner G protein–coupled receptors (GPCRs) bind ligands outside the cell and trigger events inside by selectively binding activating specific proteins. The selectivity occurs even among highly related GPCRs. For example, five subtypes of muscarinic acetylcholine (M1R to M5R) play different roles in nervous system Maeda et al. determined cryo–electron microscopy structures M1R M2R bound their respective A side-by-side comparison provided molecular understanding protein–coupling...
Abstract Single-particle cryo-electron microscopy (cryo-EM) has recently enabled high-resolution structure determination of numerous biological macromolecular complexes. Despite this progress, the application cryo-EM to G protein coupled receptors (GPCRs) in complex with heterotrimeric proteins remains challenging, owning both relative small size and limited stability these assemblies. Here we describe development antibody fragments that bind stabilize GPCR-G complexes for cryo-EM. One...
Binding of arrestin to phosphorylated G protein-coupled receptors (GPCRs) is crucial for modulating signaling. Once internalized, some GPCRs remain complexed with β-arrestins, while others interact only transiently; this difference affects GPCR signaling and recycling. Cell-based in vitro biophysical assays reveal the role membrane phosphoinositides (PIPs) β-arrestin recruitment GPCR-β-arrestin complex dynamics. We find that broadly stratify into two groups, one requires PIP binding does...
Abstract The M2 muscarinic receptor (M2R) is a prototypical G-protein-coupled (GPCR) that serves as model system for understanding GPCR regulation by both orthosteric and allosteric ligands. Here, we investigate the mechanisms governing M2R signaling versatility using cryo-electron microscopy (cryo-EM) NMR spectroscopy, focusing on physiological agonist acetylcholine supra-physiological iperoxo, well positive modulator LY2119620. These studies reveal stabilizes more heterogeneous...
Abstract The β 2 adrenergic receptor (β AR) signals through both G s and i in cardiac myocytes, the pathway counteracts pathway. However, coupling is much less efficient than most cell-based biochemical assays, making it difficult to study AR−G interactions. Here we investigate role of phospholipid composition on coupling. While negatively charged phospholipids are known enhance agonist affinity stabilize an active state AR, find that they impair i3 facilitate . Positively Ca 2+ Mg ,...
One of the largest membrane protein families in eukaryotes are G protein-coupled receptors (GPCRs). GPCRs modulate cell physiology by activating diverse intracellular transducers, prominently heterotrimeric proteins. The recent surge structural data has expanded our understanding GPCR-mediated signal transduction. However, many aspects, including existence transient interactions, remain elusive. We present cryo-EM structure light-sensitive GPCR rhodopsin complex with Gi. Our density map...
Abstract Heterotrimeric G proteins are categorized into four main families based on their function and sequence, Gs, Gi/o, Gq/11, G12/13. One receptor can couple to more than one protein subtype, the coupling efficiency varies depending GPCR-G pair. However, precise mechanism underlying different efficiencies is unknown. Here, we study structural primary secondary Gi/o coupling, using muscarinic acetylcholine type 2 (M2R) as Gi/o-coupling β -adrenergic (β AR, which primarily couples Gs)...
Human cytomegalovirus (HCMV) encodes G protein–coupled receptors (GPCRs) US28 and US27 , which facilitate viral pathogenesis through engagement of host proteins. Here we report cryo–electron microscopy structures forming nonproductive productive complexes with Gi Gq, respectively, exhibiting unusual features functional implications. The “orphan” GPCR lacks a ligand-binding pocket has captured guanosine diphosphate–bound inactive tenuous interaction. docking modes CX3CL1-US28 to favor...
A new sweet protein, named mabinlin II, was extracted with 0.5 M NaCl solution from the seeds of Capparis masaikai Lévl. and purified by ammonium sulfate fractionation, carboxymethylcellulose‐Sepharose ion‐exchange chromatography gel filtration. The sweetness II unchanged at least 48 h incubation nearly boiling temperature. Purified thus obtained gave a single band having molecular mass 14 kDa on SDS/PAGE. In presence dithiothreitol, two bands masses 4.6 5.2 Two peptides (A chain B chain)...
Connexins form a family of membrane proteins that assemble into communication channels and directly connect the cytoplasms adjoining cells. Malfunctioning connexin often cause disease, such as mutations M34T R75W in human 26, which are associated with hereditary deafness. Another residue known to be essential for normal channel activity is Cys-64. To obtain structural functional insights we studied roles these three residues by expressing mutant connexins insect Sf9 HeLa The M34A mutants...
Engineering a toxin Developing drugs that target specific subtype in G protein–coupled receptor (GPCR) family is major challenge. Maeda et al. examined the basis of specificity snake venom binding to muscarinic acetylcholine receptors (MAChRs), which mediate many functions central and parasympathetic nervous systems. They determined structure shows why mamba MT7 for one receptor, M 1 AChR, also explains how it inhibits downstream signaling. Based on this structure, they engineered be...
Phospholipids are the most abundant component in lipid membranes and essential for structural functional integrity of cell. In eukaryotic cells, phospholipids primarily synthesized de novo through Kennedy pathway that involves multiple enzymatic processes. The terminal reaction is mediated by a group cytidine-5′-diphosphate (CDP)-choline /CDP-ethanolamine-phosphotransferases (CPT/EPT) use 1,2-diacylglycerol (DAG) CDP-choline or CDP-ethanolamine to produce phosphatidylcholine (PC)...