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Mechanistic Investigations of Receptor Signaling via Canonical and Non-Canonical Amino Acid Mutagenesis


Mosesso, Richard Albert (2019) Mechanistic Investigations of Receptor Signaling via Canonical and Non-Canonical Amino Acid Mutagenesis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/X18Z-XE16.


This dissertation primarily describes investigations of the mechanisms by which pentameric ligand-gated ion channels (pLGICs) activate ("gating") using canonical and non-canonical amino acid mutagenesis. Chapter 1 provides an introduction to the systems being studied, their physiological roles, and the techniques that we have used to study them. Chapter 2 describes a series of experiments comparing the roles of amino acid residues proximal to the neurotransmitter binding site in the type 3 serotonin receptor (5-HT3R) to the aligning residues of the muscle-type nicotinic acetylcholine receptor (nAChR). The findings presented in Chapter 3 assess the functional roles of proline residues in the prokaryotic pLGIC, Erwinia ligand-gated ion channel (ELIC). Chapter 4 describes an extensive investigation of salient details of 5-HT3R gating using canonical and non-canonical amino acid mutagenesis of amino acid residues at the interface of the extracellular domain and transmembrane domain of this receptor. Chapter 5 applies a photocrosslinking strategy employing the non-canonical amino acid p-azidophenylalanine to study dimerization and cofactor interactions of the estrogen receptor α.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:biochemistry; chemical biology; protein bioscience; electrophysiology; ion channels; neuroscience; signalling; molecular biolog
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Dougherty, Dennis A.
Thesis Committee:
  • Tirrell, David A. (chair)
  • Rees, Douglas C.
  • Shapiro, Mikhail G.
Defense Date:31 May 2019
Record Number:CaltechTHESIS:06072019-131615199
Persistent URL:
Related URLs:
URLURL TypeDescription adapted for ch. 2 adapted for ch. 3
Mosesso, Richard Albert0000-0003-0927-0843
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:11713
Deposited By: Richard Mosesso
Deposited On:07 Jun 2019 22:16
Last Modified:04 Oct 2019 00:26

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