Date of Award

1-1-2013

Document Type

Dissertation

Degree Name

Ph.D.

Organizational Unit

Biological Sciences

First Advisor

Robert M. Dores, Ph.D.

Second Advisor

Joseph Angleson

Third Advisor

Nancy Lorenzon

Fourth Advisor

Todd Blankenship

Keywords

Stress response, MC2R, Melanocortin 2 receptor, ACTH, Adrenocorticotropic hormone, KKRRP, HFRW

Abstract

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.

Publication Statement

Copyright is held by the author. User is responsible for all copyright compliance.

Rights Holder

Liang Liang

Provenance

Received from ProQuest

File Format

application/pdf

Language

en

File Size

156 p.

Discipline

Biology

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