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Chemical Biology Seminar- Prof. Aaron Smith, University of Maryland, Baltimore County
April 7 @ 3:30 pm - 4:30 pm
Prof. Aaron Smith
University of Maryland, Baltimore County
Chemical Biology , Seminar
Title: “Iron Sulfur Clusters are Involved in
Abstract: Eukaryotic post-translational arginylation, mediated by the family of enzymes known as the arginine transferases (ATE1s), is an important post-translational modification that can alter protein function and even dictate cellular protein half-life. Multiple major biological pathways are linked to the fidelity of this process, including neural development, cardiovascular development, cell division, and even the stress response. Despite this significance, the structural, mechanistic, and regulatory mechanisms that govern ATE1 function remain enigmatic. Research in my lab seeks to close this gap in understanding in order to target arginylation as a future therapeutic. Intriguingly, while exploring arginine transferase function, we have discovered that ATE1s bind a previously undiscovered [Fe-S] cluster. We have used biochemical, spectroscopic, and analytical methods to decipher the composition and reactivity of this [Fe-S] cluster. Furthermore, we have used three-dimensional modeling to posit the location of cluster binding, which is confirmed by expression and purification of independent ATE1 domains. Fascinatingly, we find that ATE1 cluster-binding preserves oligomeric homogeneity while increasing arginylation efficacy, suggesting that cluster binding may regulate arginylation rates. Our data provide the framework of a cluster-based paradigm of ATE1 regulatory control, which appears to be evolutionarily conserved from yeast to mammals.