Leveraging Fic proteins as anti-microbial therapeutics
Wednesday, April 10, 2024
Abstract
Cells function by carefully orchestrating communication between proteins, often via post-translational modifications (PTMs). Dr. Mattoo’s team studies PTMs carried out by the evolutionarily conserved Fic (filamentation induced by cAMP) enzyme family. Predominant amongst these PTMs is AMPylation/adenylylation, which entails the breakdown of ATP to add an AMP to the target protein. Dr. Mattoo’s group has discovered roles for AMPylation in microbial pathogenesis and mammalian proteostatic stress response. By manipulating AMPylation, her team aims to intercept detrimental signals to promote cellular health.
Speaker Details
Dr. Seema Mattoo
Purdue University
Dr. Seema Mattoo is an Associate Professor in the Department of Biological Sciences at Purdue University, West Lafayette, IN. Her laboratory investigates the functional repertoire of Fic (filamentation induced by cAMP) proteins in regulating prokaryotic and eukaryotic signal transduction pathways. Fic proteins post-translationally modify their protein targets predominantly by adenylylation/AMPylation, which entails the covalent addition of AMP (adenosine monophosphate) to the target. AMPylation has been implicated in processes as diverse as bacterial pathogenesis, protein folding, neurodegeneration, protein translation, and cellular trafficking. Dr. Mattoo received her Ph.D. in Microbiology & Immunology from UCLA, where she studied mechanisms of Bordetella-host interactions with Dr. Jeff F. Miller. As a Howard Hughes Medical Institute Post-Doctoral Fellow with Dr. Jack Dixon at UC-San Diego, Dr. Mattoo co-discovered and characterized an amino acid motif that defines Fic proteins, and elucidated the enzymatic activity of the Fic family of enzymes as evolutionarily conserved adenylyltransferases important for bacterial pathogenesis. At Purdue, Dr. Mattoo’s laboratory identified the Hsp70 chaperone BiP and the pre-synaptic protein alpha-Synuclein as targets of AMPylation, thus establishing a role for metazoan Fic proteins in maintaining ER (endoplasmic reticulum) homeostasis and in neurodegeneration. Most recently, her lab has discovered a new clade of Fic proteins that carry out a previously unseen PTM, termed GMPylation.
