Intrinsically disordered regions facilitate Mlp1-Nab2 recognition in mRNA quality control

Quality control of mRNAs ensures that only properly processed transcripts are exported from the nucleus. Myosin-like protein 1 (Mlp1), plays a central role in this process by interacting with RNA-binding proteins (RBPs), including Nab2. While previous studies identified Phe73 in Nab2 as critical for Mlp1 binding, the molecular mechanism remains unclear. Here, we employed a computational approach to develop a mechanistic model of Mlp1-Nab2 interaction. Our results suggest that Phe73 does not act through direct contacts with Mlp1, but instead stabilizes intramolecular interactions between Nab2 helices that promote a compact conformation. F73A disrupted this helix-helix stabilization and weakened binding, whereas F73W enhanced the interaction. Our findings support a binding mechanism in which the structural flexibility of Mlp1's disordered domain enables adaptive recognition of Nab2. This mechanism may represent a general strategy by which the nuclear basket inspects mRNPs, highlighting the importance of flexible protein-protein recognition in mRNA quality control.