Characterization of the Interplay between Phosphorylation and Dimerization of RitR
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
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.
