The functional role of disordered section of proteins in mechanistic biology

A third of the human proteome is predicted to be disordered, yet these sections of the protein harbor functional relevance. The molecular mechanism of how certain enzymes and transcription factors are regulated by their own disordered sections has largely remained a mystery because of limitations in our experimental methods. Nature, however, cleverly uses these disorder segments sometimes as on/off switched and in other instances as a molecular rheostat to fine-tune the enzymatic activity, primarily through post-translation modification. The investigation proposed here demands the latest in NMR technology including those we are developing in our lab and combining them with crafty biochemistry including novel labeling schemes, and protein semi-synthesis. shed light on the molecular determinants that regulate the function. The talk will provide several examples of the "structural" aspects of how disordered proteins regulate function.