< Back to previous page

Project

Structural and thermodynamic dissection of fuzzy protein-DNA interactions in a prokaryotic transcription factor (FWOAL967)

While DNA is the book of life that forms the blueprint for a living cell or organism, proteins are the tools and machinery that make everything happen. Traditionally, protein function has been linked to protein structure, a concept that is known as the "structure-function paradigm". Protein dynamics is as important as protein structure, and in an increasing number of situations, it is observed that proteins may establish highly specific interactions without the need to fold into a unique structure. This sort of interactions that have been termed "fuzzy interaction" and occur in many different flavors..
While many fuzzy interactions have been identified in various biological contexts, the molecular and thermodynamic basis behind such modes of macromolecular recognition remains enigmatic. With very few exceptions, we do not understand how lack of structure can be compatible with tight and specific binding. Here the fuzzy interaction by a negatively charged IDP domain of a prokaryote transcription factor that does not fold upon binding, HigA from Vibrio cholerae, and its target DNA will be investigated in terms of structure and thermodynamics by a combination of integrative structural biology, protein engineering and thermodynamics. Study of this model system should lead to understanding of fuzzy yet specific recognition events from a molecular and structural viewpoint and to the development of a predictive thermodynamic model for fuzzy protein-DNA interactions
Date:1 Jan 2020 →  31 Dec 2023
Keywords:Molecular biophysics, fuzzy complexes, toxin-antitoxin module
Disciplines:Molecular biophysics, Structural biology, Transcription and translation