Date:
Wed, 05/04/201712:00-13:30
Location:
Danciger B building, Seminar room
Lecturer: Prof. Christoph Dehio
Affiliation:
Biozentrum, University of Basel, Basel, Switzerland
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 (1). The original and most abundant genuine bacterial FIC domain proteins are toxins that target bacterial topoisomerases to interfere with bacterial physiology in various, yet ill-defined, biological contexts (2). We have previously shown that Fic enzymes are autoinhibited by an α-helix (αinh) that partly obstructs the active site (3). In a first part of the talk I will discuss a peculiar system of intrinsic regulation of a subset of FIC-domain AMP-transferases by oligomerization and automodification that results in nonmonotonic concentration dependent Fic protein activity and a pronounced lag phase in the progress of target adenylylation (4). Host-targeted virulence factors have evolved repeatedly out of the pool of bacterial Fic proteins targeting topoisomerases by exaptation of the enzymatic FIC domain machinery for the manipulation of host cell signaling in favor of bacterial pathogens (1). In a second part of the talk I will reveal the extraordinary plasticity of the FIC domain in adapting in this evolutionary process to novel host targets. This will be illustrated by the convergence of Fic proteins evolved in different pathogens to modify discrete subsets of the highly conserved Rho-family GTPases, yet this is achieved by fundamentally different mechanisms of target selectivity.
References:
(1)Harms et al. (2016) Ann. Rev. Microbiol. 70:341-360.
(2)Harms et al. (2015) Cell Rep. 12:1497-1507
(3)Engel et al. (2012) Nature 482:107-110
(4)Stanger et al. (2016) PNAS 113:E529-37
Affiliation:
Biozentrum, University of Basel, Basel, Switzerland
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 (1). The original and most abundant genuine bacterial FIC domain proteins are toxins that target bacterial topoisomerases to interfere with bacterial physiology in various, yet ill-defined, biological contexts (2). We have previously shown that Fic enzymes are autoinhibited by an α-helix (αinh) that partly obstructs the active site (3). In a first part of the talk I will discuss a peculiar system of intrinsic regulation of a subset of FIC-domain AMP-transferases by oligomerization and automodification that results in nonmonotonic concentration dependent Fic protein activity and a pronounced lag phase in the progress of target adenylylation (4). Host-targeted virulence factors have evolved repeatedly out of the pool of bacterial Fic proteins targeting topoisomerases by exaptation of the enzymatic FIC domain machinery for the manipulation of host cell signaling in favor of bacterial pathogens (1). In a second part of the talk I will reveal the extraordinary plasticity of the FIC domain in adapting in this evolutionary process to novel host targets. This will be illustrated by the convergence of Fic proteins evolved in different pathogens to modify discrete subsets of the highly conserved Rho-family GTPases, yet this is achieved by fundamentally different mechanisms of target selectivity.
References:
(1)Harms et al. (2016) Ann. Rev. Microbiol. 70:341-360.
(2)Harms et al. (2015) Cell Rep. 12:1497-1507
(3)Engel et al. (2012) Nature 482:107-110
(4)Stanger et al. (2016) PNAS 113:E529-37