FICMODFUN

"FIC-Mediated Post-Translational Modifications at the Pathogen-Host Interface: Elucidating Structure, Function and Role in Infection"

 Coordinatore UNIVERSITAET BASEL 

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 Nazionalità Coordinatore Switzerland [CH]
 Totale costo 1˙699˙857 €
 EC contributo 1˙699˙857 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-ADG
 Funding Scheme ERC-AG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-02-01   -   2019-01-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    UNIVERSITAET BASEL

 Organization address address: Petersplatz 1
city: BASEL
postcode: 4003

contact info
Titolo: Dr.
Nome: Kurt
Cognome: Kamber
Email: send email
Telefono: +41 61 2672833

CH (BASEL) hostInstitution 1˙699˙857.60
2    UNIVERSITAET BASEL

 Organization address address: Petersplatz 1
city: BASEL
postcode: 4003

contact info
Titolo: Prof.
Nome: Christoph Georg Fritz
Cognome: Dehio
Email: send email
Telefono: 41612672140
Fax: 41612672118

CH (BASEL) hostInstitution 1˙699˙857.60

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 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

roles    persistent    ptms    domain    proteins    critical    functional    fic    mechanisms    adenylylation    pathogens    active    conserved    of    bartonella    functionally    site    molecular    strategy    host    attack    diverse    stealth    infection   

 Obiettivo del progetto (Objective)

'The ubiquitous FIC domain catalyzes post-translational modifications (PTMs) of target proteins; i.e. adenylylation (=AMPylation) and, more rarely, uridylylation and phosphocholination. Fic proteins are thought to play critical roles in intrinsic signaling processes of prokaryotes and eukaryotes; however, a subset encoded by bacterial pathogens is translocated via dedicated secretion systems into the cytoplasm of mammalian host cells. Some of these host-targeted Fic proteins modify small GTPases leading to collapse of the actin cytoskeleton and other drastic cellular changes. Recently, we described a large set of functionally diverse homologues in pathogens of the genus Bartonella that are required for their “stealth attack” strategy and persistent course of infection [1, 2]. Our preliminary functional analysis of some of these host-targeted Fic proteins of Bartonella demonstrated adenylylation activity towards novel host targets (e.g. tubulin and vimentin). Moreover, in addition to the canonical adenylylation activity they may also display a competing kinase activity resulting from altered ATP binding to the FIC active site. Finally, we described a conserved mechanism of FIC active site auto- inhibition that is relieved by a single amino acid exchange [1], thus facilitating functional analysis of any Fic protein of interest. Despite this recent progress only a few Fic proteins have been functionally characterized to date; our understanding of the functional plasticity of the FIC domain in mediating diverse target PTMs and their specific roles in infection thus remains limited. In this project, we aim to study the vast repertoire of host-targeted Fic proteins of Bartonella to: 1) identify novel target proteins and types of PTMs; 2) study their physiological consequences and molecular mechanisms of action; and 3) analyze structure-function relationships critical for FIC-mediated PTMs and infer from these data determinants of target specificity, type of PTM and mode of regulation. At the forefront of infection biology research, this project is ground-breaking as (i) we will identify a plethora of novel host target PTMs that are critical for a “stealth attack” infection strategy and thus will open new avenues for investigating fundamental mechanisms of persistent infection; and (ii), we will unveil the molecular basis of the remarkable functional versatility of the structurally conserved FIC domain.'

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