Intrinsic disorder codes for leaps of protein expression

Abstract

Intrinsically disordered regions (IDRs) are protein sequences lacking fixed or ordered three-dimensional structures. Many IDRs are endowed with important molecular functions such as physical interactions, posttranslational modifications or solubility enhancement. We reveal that several biologically important IDRs can act as N-terminal fusion carriers to promote target protein folding or protein quality control, thereby enhancing protein expression. This nanny function has a reasonably strong correlation with high S/T/Q/N amino acid content in IDRs and it is tunable (e.g., via phosphorylation) to regulate protein homeostasis. We propose a hypothesis that “N-terminal intrinsic disorder facilitates abundance” (NIDFA) to explain how some yeast proteins use their N-terminal IDRs (N-IDRs) to generate high levels of protein product. These N-IDRs are versatile toolkits for functional divergence in signaling and evolution.