The Intrinsically Disordered Region of Coronins Fine-tunes Oligomerization and Actin Polymerization

Coronins are highly conserved actin-binding proteins (ABPs) in the eukaryotic kingdom for polymerizing actin cytoskeleton. The biochemical activity of coronins is primarily mediated by the structural N-terminal {beta}-propeller and the C-terminal helical coiled-coil (CC) domains, but less is known about the function of a middle nonconserved region, the "unique region (UR)". The coronin UR is an intrinsically disordered region (IDR). Herein, we demonstrate that the low complexity of the UR is a conserved signature of the coronin protein family, and the UR/IDR exhibits a striking evolutionary correlated pattern associated with sequence length. By analyzing the role of the IDR in coronins via coarse-grained simulations, we reveal that evolutionary selection of IDR length is coupled with the oligomerization of IDR-containing proteins (IDPs) to provide optimal functional output. By integrating biochemical and cell biology experiments and protein engineering, we found that the IDR regulates Crn1 biochemical activity, both in vivo and in vitro, by fine-tuning CC domain oligomerization and maintaining Crn1 in a tetrameric state. The IDR-guided optimization of Crn1 oligomerization is critical for Arp2/3-mediated actin polymerization.