A5046498925- Ion Channels and Receptors
- Ion channel regulation and function
- RNA and protein synthesis mechanisms
- Neurobiology and Insect Physiology Research
- Plant Stress Responses and Tolerance
- Pancreatic function and diabetes
- Coordination Chemistry and Organometallics
- Regulation of Appetite and Obesity
- Bacterial Genetics and Biotechnology
- Research on scale insects
- Neuroscience and Neuropharmacology Research
- Biochemical Analysis and Sensing Techniques
- Lipid Membrane Structure and Behavior
- Exercise and Physiological Responses
- RNA modifications and cancer
- SARS-CoV-2 and COVID-19 Research
- Thermoregulation and physiological responses
- Meat and Animal Product Quality
- DNA and Nucleic Acid Chemistry
- Cardiac electrophysiology and arrhythmias
- DNA Repair Mechanisms
- Cellular transport and secretion
- Photoreceptor and optogenetics research
- Digital Rights Management and Security
- Bacteriophages and microbial interactions
University of Kansas Medical Center
2020-2024
University of Kansas
2020-2021
Duke University
2017-2019
Duke University Hospital
2016-2018
Duke Medical Center
2016-2018
University of Oxford
2007-2015
Clarendon College
2012
Centre for Human Genetics
2008-2009
Royal Society
2007
Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is primary cold and menthol sensor humans. We determined cryo-electron microscopy structure full-length TRPM8 from collared flycatcher at an overall resolution ~4.1 ångstroms. Our reveals three-layered architecture. The amino-terminal domain with fold distinct among known TRP structures, together carboxyl-terminal...
Transient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as key regulator normal skin physiology through release pro-inflammatory messengers. Mutations in trpv3 have been identified cause congenital disorder, Olmsted syndrome. Unlike other members thermoTRPV family, TRPV3 sensitizes upon repeated stimulation, yet lack structural information about precludes molecular-level understanding...
Neonatal diabetes is a rare monogenic form of that usually presents within the first six months life. It commonly caused by gain-of-function mutations in genes encoding Kir6.2 and SUR1 subunits plasmalemmal ATP-sensitive K+ (KATP) channel. To better understand this disease, we generated mouse expressing mutation (V59M) causes neonatal humans used Cre-lox technology to express specifically pancreatic beta cells. These beta-V59M mice developed severe soon after birth, 5 weeks age, blood...
Temperature-sensitive transient receptor potential vanilloid (thermoTRPV) channels are activated by ligands and heat, involved in various physiological processes. ThermoTRPV possess a large cytoplasmic ring consisting of N-terminal ankyrin repeat domains (ARD) C-terminal (CTD). The inter-protomer interface is unique consists CTD coiled around β-sheet which makes contacts with the neighboring ARD. Despite much existing evidence that important for thermoTRPV function, mechanism this structure...
The Transient Receptor Potential Vanilloid 2 (TRPV2) channel is a member of the temperature-sensing thermoTRPV family. Recent advances in cryo-electronmicroscopy (cryo-EM) and X-ray crystallography have provided many important insights into gating mechanisms channels. Interestingly, crystallographic studies ligand-dependent TRPV2 shown that adopts two-fold symmetric arrangements during cycle. However, it was unclear if crystal packing forces played role stabilizing arrangement channel. Here,...
Proopiomelanocortin (POMC) neurons of the hypothalamic arcuate nucleus (ARC) suppress appetite, and lack POMC-derived peptides or electrical silencing POMC causes obesity. ARC are surrounded by nerve terminals containing wakefulness-promoting orexins/hypocretins, but whether orexin affects their activity has not been tested directly. Here we identify living cells in mouse brain slices targeted expression green fluorescent protein. Using whole-cell patch-clamp recordings, show that suppresses...
Research Article12 June 2009Open Access Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and hyperinsulinism Kenju Shimomura Henry Wellcome Centre for Gene Function, Department Physiology, Anatomy Genetics, University Oxford, UK Search more papers by this author Sarah E. Flanagan Institute Biomedical Clinical Research, Peninsula Medical School, Exeter, Brittany Zadek Mark Lethby Lejla Zubcevic Christophe A. J. Girard Oliver Petz St. Vincenz Hospital Coesfeld,...
The transient receptor potential melastatin (TRPM) tetrameric cation channels are involved in a wide range of biological functions, from temperature sensing and taste transduction to regulation cardiac function, inflammatory pain, insulin secretion. structurally conserved TRPM cytoplasmic domains make up >70 % the total protein. To investigate mechanism by which contribute gating, we employed electrophysiology cryo-EM study TRPM5-a channel that primarily relies on activation via intracellular Ca
KirBac channels are prokaryotic homologs of mammalian inwardly rectifying potassium (Kir) channels, and recent structures KirBac3.1 have provided important insights into the structural basis gating in Kir channels. In this study, we demonstrate that channel activity is strongly pH-dependent, used x-ray crystallography to determine changes arise from an activatory mutation (S205L) located cytoplasmic domain (CTD). This stabilizes a novel energetically favorable open conformation which at...
Leptin is believed to exert its potent appetite-suppressing effects via stimulation of hypothalamic anorexigenic proopiomelanocortin (POMC)-containing neurons and inhibition orexigenic agouti-related protein (AgRP) neurons. We show here that at 11 mM glucose leptin excites POMC cells. At 5 glucose, however, hyperpolarizes suppresses action potential firing, by producing a greater decrease in excitatory synaptic tone than inhibitory tone. These results argue when low (5 or less) AgRP will be...
Summary Transient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as key regulator normal skin physiology through release pro-inflammatory messengers. Mutations in trpv3 have been identified cause congenital disorder, Olmsted syndrome. Unlike other members thermoTRPV family, TRPV3 sensitizes upon repeated simulation, yet lack structural information about precludes molecular-level...
Abstract Potassium channels exhibit a modular design with distinct structural and functional domains; in particular, highly conserved pore-loop sequence that determines their ionic selectivity. We now report the characterisation of novel group functionally non-selective members prokaryotic ‘inward rectifier’ subfamily K + channels. These share all key domains eukaryotic Kir/KirBac channels, but instead possess unique selectivity filter sequences unrelated to any other known filter. The...