ArticleThe Journal of biological chemistry2014
Mapping substance P binding sites on the neurokinin-1 receptor using genetic incorporation of a photoreactive amino acid.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- LEAP2 as a therapeutic target in obesity and cardiometabolic disorders.Reviews in endocrine & metabolic disorders · 2026Review
- Transient ligand contacts of the intrinsically disordered N-terminus of neuropeptide YNature communications · 2025Article
- In situ cell-surface conformation of the TCR-CD3 signaling complex.EMBO reports · 2024Article
- Noncanonical Amino Acid Tools and Their Application to Membrane Protein Studies.Chemical reviews · 2024Review
- Cracking the Code: Reprogramming the Genetic Script in Prokaryotes and Eukaryotes to Harness the Power of Noncanonical Amino Acids.Chemical reviews · 2024Review
- Association of Neurokinin-1 Receptor Signaling Pathways with Cancer.Current medicinal chemistry · 2024Review
- Inflammation and Organ Injury the Role of Substance P and Its Receptors.International journal of molecular sciences · 2023Review
- Tachykinin Receptor-Selectivity of the Potential Glioblastoma-Targeted Therapy, DOTA-[ThiInternational journal of molecular sciences · 2023Article
- Binding of Natural Peptide Ligands to the Neuropeptide YAngewandte Chemie (International ed. in English) · 2022Article
- Multiple tachykinins and their receptors characterized in the gastropod mollusk Pacific abalone: Expression, signaling cascades, and potential role in regulating lipid metabolism.Frontiers in endocrinology · 2022Article
- Structures of neurokinin 1 receptor in complex with GScience advances · 2021Article
- In Vivo, In Vitro and In Silico Studies of the Hybrid Compound AA3266, an Opioid Agonist/NK1R Antagonist with Selective Cytotoxicity.International journal of molecular sciences · 2020Article
- Capturing Peptide-GPCR Interactions and Their Dynamics.Molecules (Basel, Switzerland) · 2020Review
- Site-Specific Incorporation of Genetically Encoded Photo-Crosslinkers Locates the Heteromeric Interface of a GPCR Complex in Living Cells.Cell chemical biology · 2020Article
- Genetic code expansion and photocross-linking identify different β-arrestin binding modes to the angiotensin II type 1 receptor.The Journal of biological chemistry · 2019Article
- The Significance of NK1 Receptor Ligands and Their Application in Targeted Radionuclide Tumour Therapy.Pharmaceutics · 2019Review
- Optical control of neuronal ion channels and receptors.Nature reviews. Neuroscience · 2019Review
- Using genetically incorporated unnatural amino acids to control protein functions in mammalian cells.Essays in biochemistry · 2019Review
- Crystal structure of the human NKProceedings of the National Academy of Sciences of the United States of America · 2018Article
- Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells.Journal of visualized experiments : JoVE · 2018Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Substance P (SP) is a neuropeptide that mediates numerous physiological responses, including transmission of pain and inflammation through the neurokinin-1 (NK1) receptor, a G protein-coupled receptor. Previous mutagenesis studies and photoaffinity labeling using ligand analogues suggested that the binding site for SP includes multiple domains in the N-terminal (Nt) segment and the second extracellular loop (ECLII) of NK1. To map precisely the NK1 residues that interact with SP, we applied a novel receptor-based targeted photocross-linking approach. We used amber codon suppression to introduce the photoreactive unnatural amino acid p-benzoyl-l-phenylalanine (BzF) at 11 selected individual positions in the Nt tail (residues 11-21) and 23 positions in the ECLII (residues 170(C-10)-193(C+13)) of NK1. The 34 NK1 variants were expressed in mammalian HEK293 cells and retained the ability to interact with a fluorescently labeled SP analog. Notably, 10 of the receptor variants with BzF in the Nt tail and 4 of those with BzF in ECLII cross-linked efficiently to SP, indicating that these 14 sites are juxtaposed to SP in the ligand-bound receptor. These results show that two distinct regions of the NK1 receptor possess multiple determinants for SP binding and demonstrate the utility of genetically encoded photocross-linking to map complex multitopic binding sites on G protein-coupled receptors in a cell-based assay format.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.