In partial fulfillment of the requirements for the degree of

Doctor of Philosophy in Biology

In the

School of Biological Sciences

Xinya Su

Will defend her dissertation

Functional roles of N-terminal intrinsic disorder and phosphorylation in yeast heterotrimeric G protein gamma subunit

16, 04, 2024

12:00 PM

Marcus Nanotechnology Building, Conference Room 1117-1118

Zoom link: https://gatech.zoom.us/j/97969867691

Thesis Advisor:

Matthew Torres, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Yury Chernoff, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Ingeborg Schmidt-Krey, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Alberto Stolfi, Ph.D.

School of Biological Sciences

Georgia Institute of Technology

Amit Reddi, Ph.D.

School of Chemistry & Biochemistry

Georgia Institute of Technology

ABSTRACT: Heterotrimeric G proteins (Gabg) are essential for the transduction of extracellular signaling molecules such as chemokines, hormones, and neurotransmitters. While functional studies of G protein subunits have traditionally focused on structured regions, emerging evidence shows that intrinsically disordered protein regions (IDRs), often unresolved in protein structures, play essential roles in the signaling process. Most recently, the heterotrimeric G protein gamma subunit N-terminal tail (Gg-Nt) was identified as a hyper-regulatory IDR that controls G protein function in response to multiple extracellular stimuli. In this seminar, I will highlight foundational evidence for the role of Gg-Nt in G protein signaling and discuss three new discoveries: (1) a role for Gg subunit IDR sequence/structure in governing the balance between multiple Gbg signaling axes, (2) the identification of kinases responsible for phospho-regulatory control of Gg-Nt, and (3) the characterization of similar regulatory elements in other proteins through a proteome-wide survey. Results from these studies provide the first evidence for the intrinsic disorder as an important regulatory feature in G protein signaling and highlight the need for further understanding of phosphorylation-controlled IDRs in biology.