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Seminar D. P. Giedroc, Dep. of Chemistry, Indiana University, Bloomington, USA

Le 20/06/2018
De 16h30 à 18h00
Faculté de chimie, salle du conseil

Title:
Mechanisms of Zinc Metallostasis in Bacterial Pathogens

Abstract: First-row late d-block transition metals from Mn to Zn play critical and distinct roles in many aspects of cellular metabolism. In bacterial pathogens, metalloregulation of transcription underscores physiological adaptation to host-mediated transition metal starvation and toxicity, required to maintain metal homeostasis (metallostasis). In zinc (Zn) homeostasis, a pair of metal-sensing transcriptional repressors regulate the transcription of metal uptake and efflux transporters, where Zn typically allosterically activates or inhibits, respectively, DNA operator-promoter binding.  We have long-standing interests in the molecular underpinnings of allostery in metalloregulatory proteins, transition metal transporter function and the impact that dysregulation of the process has on cellular physiology.  In this presentation, I will discuss recent efforts to understand allostery in Zn-regulated repressors using NMR spectroscopy and companion biophysical methods, primarily focused in the Zn efflux regulator from Staphylococcus aureus, CzrA, and a Zn uptake regulator adhesin-competence repressor (AdcR) from the Gram-positive respiratory pathogen, Streptococcus pneumoniae.  These studies provide new and general insights into the evolution of allostery in these large regulatory protein families, and the role of host-imposed Zn toxicity on microbial physiology.

 For more information about the research of D. Giedroc see: http://www.indiana.edu/~dpglab/