MEMBRANE TRANSPORT: STRUCTURE-FUNCTION AND EVOLUTIONARY RELATIONSHIPS

Abstract: 

Secondary (ion gradient-driven) active transporters are crucial in both microbial adaptations and human physiology and disease. Despite recent progress with crystallography, structural modeling and genome analyses, mechanisms of such proteins remain poorly understood, mostly due to the paucity of systematic approaches to link high-resolution data with functional evidence.

Our aim is to study structure-function relationships in evolutionarily broad families of important secondary active transporters that remain mechanistically unknown to date. We will apply rationalized mutagenesis using model systems developed by us recently to address two major issues. First, how highly homologous transporters assume strikingly different specificities within the same family and, second, how distantly related transporters of different families share common binding-site architectures and motifs.

We will study: the ubiquitous but functionally diverse nucleobase-ascorbate transporter family (NCS2), focusing on key residues delineated from Cys-scanning analysis of the bacterial prototype XanQ; the distantly related nucleobase (NCS1 family) and amino acid transporters (APC superfamily) of Aspergillus nidulans with mutagenesis based on their common active-site model; molecular docking on the binding site of NCS1 transporters coupled with functional assays to reinforce design and synthesis of new antifungals; the putative nitrate/nitrite transporters of NNP family (MFS superfamily) from the first two PAH-degrading bacteria isolated in Greece and their potential use in bioremediation processes.

We expect

  1. to gain insight on side chains which underlie conserved structural and dynamic elements or dictate the evolution of new specificities between related secondary transporters,
  2. to design efficient pharmaceutical and environmental applications incorporating structure-functional analysis of transporters responsible for the uptake of the relevant toxic or nutrient compounds.

Project info

Acronym:
EVOTRANS
Coordinating Institution:
University of Ioannina
Scientific Coordinator:
Frillingos Stathis
Research Team 2 Leader:
Sophianopoulou Vicky
Research Team 3 Leader:
Pouli Nicole
Research Team 4 Leader:
Drainas Constantin

Stats

I.D.:
112
Mis:
375578
Duration (months):
45
Budget:
600 000.00
Diavgeia:
ΑΔΑ: Β4ΩΖ9-Φ7Σ

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