Date of Award

Spring 5-7-2026

Degree Type

Thesis

Degree Name

Master of Science - Natural Sciences

Department

Chemistry and Biochemistry

First Advisor

Odutayo Odunuga

Second Advisor

Bidisha Sengupta

Third Advisor

Alexandra Van-Kley

Fourth Advisor

Darrel Fry

Fifth Advisor

Violet Buhma

Abstract

The cardiac myosin–specific chaperone UNC-45B has been shown to physically interact with the cardiac myosin transcription factor GATA-4. Specifically, this interaction occurs within the chaperoning region of UNC-45B, known as the UCS domain. However, the precise nature of this interaction has not yet been fully elucidated. The present study was conducted to confirm earlier findings and to evaluate whether UNC-45B functions as a chaperone for GATA-4 using bioinformatic approaches. Analysis of the interaction using AlphaFold 3 modeling verified not only that binding occurs at the UCS (chaperoning) domain of UNC-45B, but also that the interaction is associated with an increase in α-helical structure in GATA-4. Importantly, the amino acid residues of GATA-4 that interact with UNC-45B differ from those involved in DNA binding, suggesting that regulation of GATA-4 activity is unlikely to occur through competitive inhibition by UNC-45B. Comparison across the GATA family of transcription factors revealed that variations in UNC-45B interactions are primarily located within intrinsically disordered regions rather than within the conserved zinc-finger domains or adjacent basic regions. Additionally, modeling results indicate that the GATA-4 residues involved in UNC-45B interaction closely correspond to known disease-associated mutations cataloged in the OMIM database. This finding suggests that the UNC-45B–GATA-4 interaction plays a critical role in the proper development and function of cardiac muscle.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Share

COinS

Tell us how this article helped you.

 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.