Characterization of the Interplay between Phosphorylation and Dimerization of RitR

Submitting Student(s)

Courtney Miller

Session Title

Poster Session 2

Faculty Mentor

Nicholas Grossoehme, Ph.D.

College

College of Arts and Sciences

Department

Chemistry, Physics, Geology, & the Environment

Abstract

Iron is an essential micronutrient for nearly all organisms. This metal plays a critical role in a number of physiological processes due to its ability to readily cycle between the +2 and +3 charge states, a property that also makes it a liability to the cell. Consequently, organisms have evolved dedicated machinery to control the intracellular concentration of iron. Surprisingly, S. pneumonia, an important human pathogen, lacks a well-characterized iron sensing mechanism. The repressor of iron transport (RitR), a transcriptional regulator that represses the pneumococcal iron uptake operon, appears to play a key role in controlling iron levels. Its ability to regulate transcription is impacted by oxidation-induced dimerization and kinase-induced phosphorylation; the former results in strong repression while the latter signals derepression. This project aims to better understand the relationship between oxidation, phosphorylation, and transcriptional control by RitR. Currently, efforts are focused on establishing conditions that are ideal to stabilize the RitR dimer and characterizing the oxidation/dimerization reaction. Future goals will focus on (1) the DNA binding affinity for dimer vs. monomer, (2) the impact phosphorylation has on the dimerization reaction and (3) how dimerization influences the ability of RitR to be phosphorylated.

Previously Presented/Performed?

Winthrop University Showcase of Undergraduate Research and Creative Endeavors, Rock Hill, SC, April 2023.

Type of Presentation

Poster presentation

Grant Support?

Supported by an SC-INBRE grant from the National Institute for General Medical Sciences (P20GM103499) and the U.S. Department of Education McNair Grant P217A180094.

Start Date

15-4-2023 12:00 PM

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Apr 15th, 12:00 PM

Characterization of the Interplay between Phosphorylation and Dimerization of RitR

Iron is an essential micronutrient for nearly all organisms. This metal plays a critical role in a number of physiological processes due to its ability to readily cycle between the +2 and +3 charge states, a property that also makes it a liability to the cell. Consequently, organisms have evolved dedicated machinery to control the intracellular concentration of iron. Surprisingly, S. pneumonia, an important human pathogen, lacks a well-characterized iron sensing mechanism. The repressor of iron transport (RitR), a transcriptional regulator that represses the pneumococcal iron uptake operon, appears to play a key role in controlling iron levels. Its ability to regulate transcription is impacted by oxidation-induced dimerization and kinase-induced phosphorylation; the former results in strong repression while the latter signals derepression. This project aims to better understand the relationship between oxidation, phosphorylation, and transcriptional control by RitR. Currently, efforts are focused on establishing conditions that are ideal to stabilize the RitR dimer and characterizing the oxidation/dimerization reaction. Future goals will focus on (1) the DNA binding affinity for dimer vs. monomer, (2) the impact phosphorylation has on the dimerization reaction and (3) how dimerization influences the ability of RitR to be phosphorylated.