The intrinsically disordered region of coronins fine-tunes oligomerization and actin polymerization

Coronins play critical roles in actin network formation. The diverse functions of coronins are regulated by the structured N-terminal β propeller and the C-terminal coiled coil (CC). However, less is known about a middle “unique region” (UR), which is an intrinsically disordered region (IDR). The UR/IDR is an evolutionarily conserved signature in the coronin family. By integrating biochemical and cell biology experiments, coarse-grained simulations, and protein engineering, we find that the IDR optimizes the biochemical activities of coronins in vivo and in vitro. The budding yeast coronin IDR plays essential roles in regulating Crn1 activity by fine-tuning CC oligomerization and maintaining Crn1 as a tetramer. The IDR-guided optimization of Crn1 oligomerization is critical for F-actin cross-linking and regulation of Arp2/3-mediated actin polymerization. The final oligomerization status and homogeneity of Crn1 are contributed by three examined factors: helix packing, the energy landscape of the CC, and the length and molecular grammar of the IDR. [Display omitted] •IDR fine-tunes coiled-coil-mediated protein oligomerization•Oligomerization states determine coronin’s biochemical activities and functions•IDR’s molecular grammar and length influence coronin oligomerization Han et al. found that an intrinsically disordered region (IDR) optimizes coronin activity. The IDR fine-tunes the oligomerization of the neighboring coiled coil, maintaining coronins in a tetrameric state crucial for F-actin cross-linking and Arp2/3-mediated actin polymerization. Three factors contribute to coronin oligomerization: helix packing, coiled-coil energy landscape, and the IDR’s length and sequence.