Date of Award
1-1-2018
Document Type
Dissertation
Degree Name
Ph.D.
Organizational Unit
Biological Sciences
First Advisor
Robert M. Dores, Ph.D.
Second Advisor
Phil Danielson
Third Advisor
Joseph Angleson
Fourth Advisor
James Fogleman
Keywords
Alanine substitution, Chimeric receptor, MC2R, Melanocortin-2 receptor, Melanocortin receptor accessory protein 1, MRAP1
Abstract
The melanocortin-2 receptor (MC2R) is the most complex due to its trafficking and ligand selectivity requirements for proper activation. The MC2R requires the melanocortin receptor accessory protein-1 (MRAP1) for proper trafficking and activation of the receptor by the melanocortin hormone, ACTH. MRAP1 is a single transmembrane-spanning domain protein that creates a homodimer with another MRAP1 protein. Furthermore, MRAP2 creates a heterodimer with the MC2R. Previous studies have shown that the MRAP1 protein contains an activation motif required for activation of MC2R and this activation motif located on the extracellular space side of the plasma membrane of the cell. The objective of this dissertation was to analyze potential contact sites between the extracellular space side activation motif of MRAP1 with the extracellular domains of the MC2R—the N-terminal, extracellular loop 1, extracellular loop 2, and extracellular loop 3. This analysis utilized a chimeric protein paradigm as well as alanine substitution experiments to observe potential contact sites between MRAP1 and the MC2R. By using these approaches, important residues required for trafficking or activation were identified in transmembrane 4, extracellular loop 2, and transmembrane 5 domains for MC2R. These results propose a revised mechanism for MC2R activation. Finally, the revised model suggests evolutionary implications for vertebrate MC2R activation.
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Perry Victoria Davis
Provenance
Received from ProQuest
File Format
application/pdf
Language
en
File Size
92 p.
Recommended Citation
Davis, Perry Victoria, "Evaluating the Interaction Between the Human Melanocortin-2 Receptor and the Accessory Protein, Mrap1: Chimeric Receptor and Alanine Substitution Studies on Transmembrane Domain 4, Extracellular Loop 2, and Transmembrane Domain 5" (2018). Electronic Theses and Dissertations. 1530.
https://digitalcommons.du.edu/etd/1530
Copyright date
2018
Discipline
Cellular biology