ArticleJournal of the American Chemical Society2012
Functionally important aromatic-aromatic and sulfur-π interactions in the D2 dopamine receptor.
Article in Journal of the American Chemical Society, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 116 citations in OpenAlex.
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- The C-terminus is essential for the stability of the mycobacterial channel protein MspA.Protein science : a publication of the Protein Society · 2024Article
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- Tuning phenylalanine fluorination to assess aromatic contributions to protein function and stability in cells.Nature communications · 2023Article
- The Role of Tryptophan in π Interactions in Proteins: An Experimental Approach.Journal of the American Chemical Society · 2022Article
- Semi-Synthesis ofMolecules (Basel, Switzerland) · 2022Article
- Structural characterization of the ANTAR antiterminator domain bound to RNA.Nucleic acids research · 2022Article
- Comparative Analysis of Sulfonium-π, Ammonium-π, and Sulfur-π Interactions and Relevance to SAM-Dependent Methyltransferases.Journal of the American Chemical Society · 2022Article
- An "up" oriented methionine-aromatic structural motif in SUMO is critical for its stability and activity.The Journal of biological chemistry · 2021Article
- In silico investigation of potential inhibitors to main protease and spike protein of SARS-CoV-2 in propolis.Biochemistry and biophysics reports · 2021Article
- Contributions of methionine to recognition of trimethyllysine in aromatic cage of PHD domains: implications of polarizability, hydrophobicity, and charge on binding.Chemical science · 2021Article
- Dopamine DInternational journal of molecular sciences · 2021Article
- Highly Photostable and Luminescent Donor-Acceptor Molecules for Ultrasensitive Detection of Sulfur Mustard.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Shrinking of repeating unit length in leucine-rich repeats from double-stranded DNA viruses.Archives of virology · 2021Article
- NTRK kinase domain mutations in cancer variably impact sensitivity to type I and type II inhibitors.Communications biology · 2020Article
- The functional role of the αM4 transmembrane helix in the muscle nicotinic acetylcholine receptor probed through mutagenesis and coevolutionary analyses.The Journal of biological chemistry · 2020Article
- Does Cysteine Rule (CysR) Complete the CendR Principle? Increase in Affinity of Peptide Ligands for NRP-1 Through the Presence of N-Terminal Cysteine.Biomolecules · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The recently published crystal structure of the D3 dopamine receptor shows a tightly packed region of aromatic residues on helices 5 and 6 in the space bridging the binding site and what is thought to be the origin of intracellular helical motion. This highly conserved region also makes contacts with residues on helix 3, and here we use double mutant cycle analysis and unnatural amino acid mutagenesis to probe the functional role of several residues in this region of the closely related D2 dopamine receptor. Of the eight mutant pairs examined, all show significant functional coupling (Ω > 2), with the largest coupling coefficients observed between residues on different helices, C3.36/W6.48, T3.37/S5.46, and F5.47/F6.52. Additionally, three aromatic residues examined, F5.47, Y5.48, and F5.51, show consistent trends upon progressive fluorination of the aromatic side chain. These trends are indicative of a functionally important electrostatic interaction with the face of the aromatic residue examined, which is likely attributed to aromatic-aromatic interactions between residues in this microdomain. We also propose that the previously determined fluorination trend at W6.48 is likely due to a sulfur-π interaction with the side chain of C3.36. We conclude that these residues form a tightly packed structural microdomain that connects helices 3, 5, and 6, thus forming a barrier that prevents dopamine from binding further toward the intracellular surface. Upon activation, these residues likely do not change their relative conformation, but rather act to translate agonist binding at the extracellular surface into the large intracellular movements that characterize receptor activation.
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