Proteins are dynamic biomolecules which undergo structural fluctuations to adopt multiple conformations while performing important biological functions. A wide range of debilitating human diseases such as Alzheimer's,Huntington's and Parkinson's disease arise from protein misfolding and aggregation. Intrinsically disordered proteins are frequently implicated in misfolding events due to lack of their well defined structure. These proteins demonstrate structural plasticity by coupling their folding to binding appropriate ligand. In this coupled folding binding process, protein domains that are disordered in solution, adopt well defined structures upon binding a ligand. In this work we employed protein topology based Go-model simulations to study the coupled folding binding mechanism for the disordered C-terminal domain of the phosphatase protein(FCP1) to bind the ordered RAP74 subunit of the transcription factor protein (TFIIF). These simulations predict that the disordered FCP1 adopts partially folded structure prior to binding and complete its folding upon binding RAP74.

Molecular principles of coupled folding and binding

244th National Meeting (2012)

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