title: Biological Diversity and Molecular Plasticity of FIC Domain Proteins.
abstract: The ubiquitous proteins with FIC (filamentation induced by cyclic AMP) domains use a conserved enzymatic machinery to modulate the activity of various target proteins by posttranslational modification, typically AMPylation. Following intensive study of the general properties of FIC domain catalysis, diverse molecular activities and biological functions of these remarkably versatile proteins are now being revealed. Here, we review the biological diversity of FIC domain proteins and summarize the underlying structure-function relationships. The original and most abundant genuine bacterial FIC domain proteins are toxins that use diverse molecular activities to interfere with bacterial physiology in various, yet ill-defined, biological contexts. Host-targeted virulence factors have evolved repeatedly out of this pool by exaptation of the enzymatic FIC domain machinery for the manipulation of host cell signaling in favor of bacterial pathogens. The single human FIC domain protein HypE (FICD) has a specific function in the regulation of protein stress responses.
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland; email: alexander.harms@unibas.ch , frederic.stanger@unibas.ch , christoph.dehio@unibas.ch.
authors.forename: Alexander
authors.initials: A
authors.lastname: Harms
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland; email: alexander.harms@unibas.ch , frederic.stanger@unibas.ch , christoph.dehio@unibas.ch.|Focal Area Structural Biology and Biophysics, Biozentrum, University of Basel, CH-4056 Basel, Switzerland.|*Current address: Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Frédéric V
authors.initials: FV
authors.lastname: Stanger
authors.affiliation: Focal Area Infection Biology, Biozentrum, University of Basel, CH-4056 Basel, Switzerland; email: alexander.harms@unibas.ch , frederic.stanger@unibas.ch , christoph.dehio@unibas.ch.
authors.forename: Christoph
authors.initials: C
authors.lastname: Dehio
mesh_terms: D001419:Bacteria / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D044822:Biodiversity; D014644:Genetic Variation; D008958:Models, Molecular; D000072417:Protein Domains
chemical_list: D001426:Bacterial Proteins
keywords: AMPylation; adenylylation; bacterial effector protein; bacterial evolution; posttranslational modification; toxin-antitoxin module