Extended Data Fig. 4: Computational simulation reveals that the IDR regions of SE and MTB mediate the protein-protein interaction.
From: SERRATE drives phase separation behaviours to regulate m6A modification and miRNA biogenesis
a – f, Computational simulation via IUPred3 (a – c) and AlphaFold2 (d – f) showed disorder regions of animal (a, b) and plant m6A writers (c – e), and plant SE (f). For IUPred3 analysis, a window size of 30 consecutive residues was used. The predicted disordered and ordered regions are presented in red and blue, respectively. The left y-axis represents the tendency score, while the x-axis represents positions of amino acids. ZF, zinc finger; MTD, methyltransferase ___domain. g, h, 3D models of heterotypic assembly, including a human-MTC mimicking structure of MTA-MTB (g), and an IDR-coupled folding model of SE-MTB (h). Both models were predicted via the multimer module of AlphaFold2. The different entities are color-coded as indicated. In (h), the N-terminal IDR of MTB wrapped around the C-terminal IDR of SE to create a pivotal interaction interface which served as the nexus of the MTB-SE assembly, which was further stabilized by the N-terminal IDR of SE clasping MTB. Furthermore, the MTase ___domain of MTB and the zinc finger ___domain of SE maintained a functionally active conformation like that of MTC or the monomer, respectively. i, Sequence alignment of C-terminal of SE and its homologs across different species showed that R718 is conserved through plants. Predicted seven donors of hydrogen bonds in the SE-MTB interaction were highlighted in dashed boxes.
