A5003400108- Receptor Mechanisms and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Bone health and treatments
- Parathyroid Disorders and Treatments
- Metabolism, Diabetes, and Cancer
- HIV Research and Treatment
- Neuropeptides and Animal Physiology
- Mosquito-borne diseases and control
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Malaria Research and Control
- Infant Nutrition and Health
- Bone health and osteoporosis research
- Pancreatic function and diabetes
- Blood disorders and treatments
- Chemical Synthesis and Analysis
- Thyroid Disorders and Treatments
- PI3K/AKT/mTOR signaling in cancer
- Genetic Syndromes and Imprinting
- Monoclonal and Polyclonal Antibodies Research
- Fibroblast Growth Factor Research
- Vitamin D Research Studies
- Pancreatic and Hepatic Oncology Research
University of Pittsburgh
2021-2025
Walter Reed Army Institute of Research
2022
The mechanism determining the preferential stimulation of one heterotrimeric G protein signaling pathway over another by a ligand remains undetermined. By reporting cryogenic electron microscopy (cryo-EM) structure parathyroid hormone (PTH) type 1 receptor (PTH1R) complexed with Gq and comparing its allosteric dynamics that PTH1R in complex s , we uncover underlying such preferences. We show an coupling between PTH C-terminal helix α5 Gα subunit controls stability specific protein, or q ....
Abstract The Circumsporozoite Protein (CSP) of Plasmodium falciparum contains an N-terminal region, a conserved Region I (RI), junctional 25–42 copies major (NPNA) and minor repeats followed by C-terminal domain. recently approved malaria vaccine, RTS,S/AS01 NPNAx19 the region CSP. efficacy RTS,S against natural infection is low short-lived, mapping epitopes inhibitory monoclonal antibodies may allow for rational improvement CSP vaccines. Tobacco Mosaic Virus (TMV) was used here to display...
The parathyroid hormone (PTH)–related protein (PTHrP) is indispensable for the development of mammary glands, placental calcium ion transport, tooth eruption, bone formation and remodeling, causes hypercalcemia in patients with malignancy. Although mature forms PTHrP body consist splice variants 139, 141, 173 amino acids, our current understanding on how endogenous transduces signals through its cognate G-protein coupled receptor (GPCR), PTH type 1 (PTHR), largely derived from studies done...
G protein-coupled receptors (GPCR) and glycosaminoglycans (GAGs) are two essential components of the cell surface that regulate physiological processes in body. GPCRs most extensive family transmembrane control cellular responses to extracellular stimuli, while GAGs polysaccharides contribute function matrix (ECM). Due their proximity plasma membrane, participate signal transduction by interacting with various molecules receptors. can directly interact certain or ligands (chemokines, peptide...
Abstract The parathyroid hormone receptor type 1 (PTH1R) is a G protein-coupled that plays key roles in regulating calcium homeostasis and skeletal development via binding the ligands, PTH PTH-related protein (PTHrP), respectively. Eiken syndrome rare disease of delayed bone mineralization caused by homozygous PTH1R mutations. Of three mutations identified so far, R485X, truncates C-terminal tail, while E35K Y134S alter residues receptor’s amino-terminal extracellular domain. Here, using...
<b>Abstract ID 93645</b> <b>Poster Board 151</b> G protein-coupled receptors (GPCRs) mediate temporally-precise transmission of signals from the extracellular milieu to cytoplasm. Gαs is prototypical signal transducer in cytoplasm activated by GPCRs, and activating mutations render it an oncogene various types cancer. Despite emerging evidence on importance signaling compartmentalization within cells its role cancer, there paucity genetic pharmacological tools capable dissecting with...
<b>Abstract ID 84617</b> <b>Poster Board 142</b> Defects in parathyroid gland function due to reduced calcium-sensing receptor (CaSR) expression or activity cells results primary hyperparathyroidism (PHPT), where hormone (PTH) hypersecretion perturbs calcium (Ca<sup>2+</sup>) homeostasis by increasing serum Ca<sup>2+</sup> abnormal levels (i.e., hypercalcemia). Subsequently, hypercalcemia multi-organ symptoms and failure bone (osteoporosis), kidney (nephrocalcinosis), muscle (weakness),...
Abstract Disclosure: C. Tu: None. Z. Cheng: K.A. Pena: S. Savransky: T. Glinin: N. Szeto: J.A. Sosa: Research Investigator; Self; Institutional research funding and Data Monitoring Committee of the Medullary Thyroid Cancer Consortium Registry, supported by, AstraZeneca, Novo Nordisk, Eli Lilly & Company, Exelixis, Inc.. J. Vilardaga: Koh: W. Chang: Primary hyperparathyroidism (PHPT) is a common endocrinopathy characterized by elevated parathyroid hormone (PTH) secretion. Low serum...
Abstract The assembly of a peptide ligand, its receptor, and β-arrestin (βarr) into ternary complex within the cell membrane is crucial aspect G protein-coupled receptor (GPCR) signaling. We explore this by attaching fluorescent moieties to parathyroid hormone (PTH) type 1 (PTH R), using PTH as prototypical hormone, along with βarr clathrin, recording dual-color single-molecule imaging at plasma live cells. Here we show that R exhibits near-Brownian diffusion, whereas unbound displays...
The parathyroid hormone (PTH) type 1 receptor (PTHR) regulates a variety of key biological processes, including mineral ion and bone homeostasis, through the action its two natural peptide ligands: PTH PTH-related (PTHrP). Particularly, PTHrP is indispensable for development mammary glands, placental calcium transport, tooth eruption, formation remodeling. Although mature forms PTHR ligands consist 84 141/173 amino acids PTHrP, respectively, our current understanding on how endogenous...