Dopamine receptors D1R and D2R form a heterooligomeric complex with signaling properties distinct from the individual receptors. Aberrant expression of this protein-protein complex is linked to the etiology of various neuropsychiatric diseases. Formation of the D1R-D2R heteromer is thought to be dependent upon electrostatic interactions occurring between the carboxyl tail of D1R and the third intracellular loop of D2R. Using this interaction site as template, I synthesized several peptides designed to disrupt the minimal area of the D1R-D2R interaction interface and tested these using whole cell lysates of human brain tissue and dopamine receptor constructs. I report that a synthetic peptide with the sequence EAARRAQE is efficient in blocking D1R-D2R interaction, while shorter and more highly charged peptides (EERRAQ, ARRA and AARRAQ) had no effect. This research provides insight into the binding regions involved in D1-D2 heteromer formation, and may aid future drug development efforts that target this receptor complex.
","abstract_html":"<p>Dopamine receptors D1R and D2R form a heterooligomeric complex with signaling properties distinct from the individual receptors. Aberrant expression of this protein-protein complex is linked to the etiology of various neuropsychiatric diseases. Formation of the D1R-D2R heteromer is thought to be dependent upon electrostatic interactions occurring between the carboxyl tail of D1R and the third intracellular loop of D2R. Using this interaction site as template, I synthesized several peptides designed to disrupt the minimal area of the D1R-D2R interaction interface and tested these using whole cell lysates of human brain tissue and dopamine receptor constructs. I report that a synthetic peptide with the sequence EAARRAQE is efficient in blocking D1R-D2R interaction, while shorter and more highly charged peptides (EERRAQ, ARRA and AARRAQ) had no effect. This research provides insight into the binding regions involved in D1-D2 heteromer formation, and may aid future drug development efforts that target this receptor complex.</p>","abstract_has_math":false,"creators":["Champion, Margaret M."],"institution":null,"degree_name":"Master of Science (MS)","degree_level":"Open Access Thesis","degree_discipline":"Chemistry","degree_department":null,"school":null,"contributors":["Hedeel Evans, PhD","Deborah Heyl-Clegg, PhD","Jeffery Guthrie, PhD"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-01-01T08:00:00Z","date_published":"2019-01-01T08:00:00Z","updated_at":"2026-07-24T02:17:33Z","subjects":["D1R-D2R","dopamine","gpcr receptor heteromers","Biochemistry"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://commons.emich.edu/theses/988","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hedeel Evans, PhD","Deborah Heyl-Clegg, PhD","Jeffery Guthrie, PhD"]},{"key":"dc:creator","label":"Author","values":["Champion, Margaret M."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2019-09-26T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Open Access Thesis"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Master of Science (MS)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["D1R-D2R","dopamine","gpcr receptor heteromers","Biochemistry"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://commons.emich.edu/theses/988"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Dopamine receptors D1R and D2R form a heterooligomeric complex with signaling properties distinct from the individual receptors. Aberrant expression of this protein-protein complex is linked to the etiology of various neuropsychiatric diseases. Formation of the D1R-D2R heteromer is thought to be dependent upon electrostatic interactions occurring between the carboxyl tail of D1R and the third intracellular loop of D2R. Using this interaction site as template, I synthesized several peptides designed to disrupt the minimal area of the D1R-D2R interaction interface and tested these using whole cell lysates of human brain tissue and dopamine receptor constructs. I report that a synthetic peptide with the sequence EAARRAQE is efficient in blocking D1R-D2R interaction, while shorter and more highly charged peptides (EERRAQ, ARRA and AARRAQ) had no effect. This research provides insight into the binding regions involved in D1-D2 heteromer formation, and may aid future drug development efforts that target this receptor complex.
"]},{"key":"dc:title","label":"Title","values":["Unravelling the D1R-D2R heteromer"]}]}],"canonical_facts":{"dc:contributor":["Hedeel Evans, PhD","Deborah Heyl-Clegg, PhD","Jeffery Guthrie, PhD"],"dc:creator":["Champion, Margaret M."],"dc:date.available":["2019-09-26T07:00:00Z"],"dc:description.abstract":["Dopamine receptors D1R and D2R form a heterooligomeric complex with signaling properties distinct from the individual receptors. Aberrant expression of this protein-protein complex is linked to the etiology of various neuropsychiatric diseases. Formation of the D1R-D2R heteromer is thought to be dependent upon electrostatic interactions occurring between the carboxyl tail of D1R and the third intracellular loop of D2R. Using this interaction site as template, I synthesized several peptides designed to disrupt the minimal area of the D1R-D2R interaction interface and tested these using whole cell lysates of human brain tissue and dopamine receptor constructs. I report that a synthetic peptide with the sequence EAARRAQE is efficient in blocking D1R-D2R interaction, while shorter and more highly charged peptides (EERRAQ, ARRA and AARRAQ) had no effect. This research provides insight into the binding regions involved in D1-D2 heteromer formation, and may aid future drug development efforts that target this receptor complex.
"],"dc:identifier":["https://commons.emich.edu/theses/988"],"dc:subject":["D1R-D2R","dopamine","gpcr receptor heteromers","Biochemistry"],"dc:title":["Unravelling the D1R-D2R heteromer"],"thesis:degree_discipline":["Chemistry"],"thesis:degree_level":["Open Access Thesis"],"thesis:degree_name":["Master of Science (MS)"]},"updated_at":"2026-07-24T02:17:33Z"}