Extracellular domains of the neurokinin-1 receptor: Structural characterization and interactions with substance P
| Autor: | Andrea Piserchio, Amy L. Ulfers, Dale F. Mierke |
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| Rok vydání: | 2002 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Molecular model Biophysics Substance P Biochemistry Protein Structure Secondary Biomaterials Protein structure GTP-Binding Proteins Tachykinin receptor 1 Animals Amino Acid Sequence G protein-coupled receptor Binding Sites Photoaffinity labeling biology Chemistry Organic Chemistry General Medicine Receptors Neurokinin-1 Peptide Fragments Rats Transmembrane domain Membrane protein Rhodopsin biology.protein Extracellular Space |
| Zdroj: | Biopolymers. 66:339-349 |
| ISSN: | 1097-0282 0006-3525 |
| DOI: | 10.1002/bip.10312 |
| Popis: | The technical difficulties associated with the structure determination of membrane proteins have limited the structural information available for the ligand binding to G-protein coupled receptors (GPCRs). Here, we describe a reductionist approach to GPCR structure determination in which the extracellular domains of the receptor are examined by high-resolution NMR in the presence of a membrane mimetic. The resulting structural features are then incorporated into a molecular model of the receptor, utilizing the x-ray structure of rhodopsin to generate the topological orientation of the transmembrane helices. The results of our study of the neurokinin-1 receptor (NK-1R) and its interactions with substance P (SP) are detailed here. The structure of the N-terminus, NK-1R(1-39), and of the third extracellular loop, NK-1R(264-290), in the presence of dodecylphosphocholine micelles is described. Our findings provide a structural basis for the interpretation of the results from other methods including mutagenesis, fluorescence, and photoaffinity labeling experiments, resulting in an experimentally based, high-resolution model of SP binding to NK-1R. |
| Databáze: | OpenAIRE |
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