A5046478733- Connexins and lens biology
- Nicotinic Acetylcholine Receptors Study
- Advanced Electron Microscopy Techniques and Applications
- Lipid Membrane Structure and Behavior
- RNA and protein synthesis mechanisms
- Ion channel regulation and function
- Adenosine and Purinergic Signaling
- Yersinia bacterium, plague, ectoparasites research
- Heat shock proteins research
- RNA modifications and cancer
- Gastroesophageal reflux and treatments
- RNA Research and Splicing
- Birth, Development, and Health
- Biomedical Research and Pathophysiology
- Bacillus and Francisella bacterial research
- Nanopore and Nanochannel Transport Studies
- Inflammatory mediators and NSAID effects
- Pregnancy and preeclampsia studies
- Bipolar Disorder and Treatment
- Ion Transport and Channel Regulation
- Hearing Loss and Rehabilitation
- Vestibular and auditory disorders
- Magnesium in Health and Disease
- Pharmacological Receptor Mechanisms and Effects
- Mass Spectrometry Techniques and Applications
Forschungszentrum Jülich
2022-2023
Portland State University
2018-2022
Western Washington University
2017
Abstract Gap junctions establish direct pathways for cells to transfer metabolic and electrical messages. The local lipid environment is known affect the structure, stability intercellular channel activity of gap junctions; however, molecular basis these effects remains unknown. Here, we incorporate native connexin-46/50 (Cx46/50) channels into a dual nanodisc system, mimicking cell-to-cell junction. Structural characterization by CryoEM reveals lipid-induced stabilization channel, resulting...
Key points Gap junctions formed by different connexins are expressed throughout the body and harbour unique channel properties that have not been fully defined mechanistically. Recent structural studies cryo‐electron microscopy produced high‐resolution models of related but functionally distinct lens (Cx50 Cx46) captured in a stable open state, opening door for structure–function comparison. Here, we conducted comparative molecular dynamics simulation electrophysiology to dissect...
Abstract The outstanding acuity of the mammalian ear relies on cochlear amplification, an active mechanism based electromotility (eM) outer hair cells. eM is a piezoelectric generated by little-understood, voltage-induced conformational changes anion transporter homolog prestin (SLC26A5). We used combination molecular dynamics (MD) simulations and biophysical approaches to identify structural that mediate eM. MD showed samples vast landscape with expanded (ES) compact (CS) states beyond...
Introduction: The P2X3 receptor (P2X3R), an ATP-gated non-selective cation channel of the P2X family, is expressed in sensory neurons and involved nociception. P2X3R inhibition was shown to reduce chronic neuropathic pain. In a previous screening 2000 approved drugs, natural products, bioactive substances, various non-steroidal anti-inflammatory drugs (NSAIDs) were found inhibit P2X3R-mediated currents. Methods: To investigate whether receptors contributes analgesic effect NSAIDs, we...
Pseudohypoaldosteronism type II (PHA II) is a Mendelian disorder, featuring hyperkalemic acidosis and low plasma renin levels, typically associated with hypertension. Mutations in WNK1, WNK4, CUL3, KLHL3 cause PHA II, dominant mutations CUL3 either or recessive KLHL3. Fourteen families have been reported, diagnosis at the age of 3 months to 56 years, individuals normal kidney function.We performed clinical genetic investigations patient hypertension used molecular dynamics simulations,...
Abstract Gap junctions establish direct pathways for connected cells and tissues to transfer metabolic electrical messages 1 . The local lipid environment is known affect the structure, stability intercellular channel activity of gap 2-5 ; however, molecular basis these effects remains unknown. To gain insight toward how interact with their membrane environment, we used nanodisc technology incorporate native connexin-46/50 (Cx46/50) channels into a dual system, closely mimicking cell-to-cell...
Journal Article Visualization of Protein-Lipid Interactions in Connexin-46/50 Intercellular Communication Channels at 2.1 Å Resolution Get access Jonathan A Flores, Flores Department Chemistry, Portland State University, Portland, OR, USADepartment Biochemistry and Molecular Biology, Oregon Health Science USA Search for other works by this author on: Oxford Academic Google Scholar Kimberly Dolan, Dolan Bassam G Haddad, Haddad Janette B Myers, Myers Craig C Yoshioka, Yoshioka Biomedical...
Abstract The connexins form intercellular communication channels, known as gap junctions (GJs), that facilitate diverse physiological roles in vertebrate species, ranging from electrical coupling and long-range chemical signaling, to coordinating development nutrient exchange. GJs formed by different are expressed throughout the body harbor unique channel properties have not been fully defined mechanistically. Recent structural studies implicated amino-terminal (NT) domain contributing...