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Structure and function of prokaryotic membrane permeases and pores and of a two-component response regulator

English title Structure and function of prokaryotic membrane permeases and pores and of a two-component response regulator
Applicant Schirmer Tilman
Number 105587
Funding scheme Project funding (Div. I-III)
Research institution Abteilung Strukturbiologie und Biophysik Biozentrum Universität Basel
Institution of higher education University of Basel - BS
Main discipline Structural Research
Start/End 01.10.2004 - 31.03.2011
Approved amount 798'332.00
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Keywords (7)

Membrane proteins; protein crystallography; structural biology; membrane transport; c-di-GMP signaling; diguanylate cyclase; antibiotics

Lay Summary (English)

Lead
Lay summary
Our aim is to contribute to the understanding, on the molecular level, of the mechanisms by which proteins perform their action. To this aim, we are combining X-ray structure analysis, functional characterization and site-directed mutagenesis. In this project, we are working on two problems.(I) How are small water soluble molecules translocated across the bacterial cell wall? Over the years we have been working on the structure elucidation of bacterial porins, integral membrane proteins that form hydrophilic pores in the outer membrane, and have analyzed structure - function relationships. Currently, we are analyzing KdgM from Erwinia crysanthemi, the causative agent of fire blight ("Feuerbrand"). This porin allows the bacteria to feed on degradation products of plants. Blockage of the pore by specific inhibitors designed based on the structure may be a way to combat this disease. Moreover, the structure will contribute to our scarce knowledge about membrane protein structures.(II) What are the players and the mechanisms that employ bacteria in c-di-GMP signaling? C-di-GMP, a small molecule "Botenstoff" or second messenger, has only recently been discovered to be present in all bacteria and to regulate the formation of cell surface features such as switching between a motile lifestyle (formation of a flagellum) and a sessile lifestyle (formation of a stalk). C-di-GMP has also been shown to be involved in the formation of biofilms, which is a bacterial strategy to evade recognition by the immune system. We have gained insight into the catalytic and regulatory mechanisms of a diguanylate cyclase, by solving crystal structures of this enzyme that catalyzes the production of c-di-GMP. We are striving to contribute more structural knowledge about proteins involved in c-di-GMP signaling. In this way, we want to add to the knowledge about second messenger signaling in general, but also contribute to the identification of a novel antibiotic target.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

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Associated projects

Number Title Start Funding scheme
138414 Molecular mechanisms of c-di-GMP signaling and of target AMPylation 01.02.2012 Project funding (Div. I-III)
53727 Crystallography of membrane proteins that enable solute trans- location 01.04.1999 Project funding (Div. I-III)
127433 Mechanisms of cyclic di-GMP signaling 01.02.2010 Sinergia

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