Evolution of Melanocortin-2 Receptor Activations: Studies on a Mammal and a Fish

<p>The structure and function relationship between melanocortin-2 receptor (MC2R) and ACTH are the most complicated in melanocortin receptor gene family. A comparative study on the activation of human and rainbow trout MC2R will provide a useful model system for understanding how ACTH emerged as the sole ligand for the MC2R of bony vertebrates. This dissertation will discuss how studies utilizing analogs of hACTH(1-24) have revealed two critical amino acid motifs in this ligand (HFRW and KKRRP) which are required for the activation of MC2R. In addition, the KKRRP motif functioned as the unique binding site for MC2R that directly contributes to the ligand selectivity feature, as revealed from studies on an ACTH antagonist which exclusively targets MC2R. Finally, based on our model for the interaction of ACTH and MC2R, the amino acid residues within TM4, EC2, and TM5 domains responsible for ACTH ligand selectivity will be evaluated by site-directed mutagenesis studies.</p>

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Year dc:date.available

2013

Author dc:creator

• Liang, Liang

Contributors dc:contributor

• Robert M. Dores, Ph.D.
• Joseph Angleson
• Nancy Lorenzon
• Todd Blankenship

• Stress response
• MC2R
• Melanocortin 2 receptor
• ACTH
• Adrenocorticotropic hormone
• KKRRP
• HFRW
• Biology

Statement dc:rights

• <p>Copyright is held by the author. User is responsible for all copyright compliance.</p>

Language dc:language

en

Repository record dc:identifier

https://digitalcommons.du.edu/etd/983

OAI identifier oai:identifier

oai:digitalcommons.du.edu:etd-1982