| First Author | Mouilleron S | Year | 2008 |
| Journal | EMBO J | Volume | 27 |
| Issue | 23 | Pages | 3198-208 |
| PubMed ID | 19008859 | Mgi Jnum | J:142795 |
| Mgi Id | MGI:3822206 | Doi | 10.1038/emboj.2008.235 |
| Citation | Mouilleron S, et al. (2008) Molecular basis for G-actin binding to RPEL motifs from the serum response factor coactivator MAL. EMBO J 27(23):3198-208 |
| abstractText | Serum response factor transcriptional activity is controlled through interactions with regulatory cofactors such as the coactivator MAL/MRTF-A (myocardin-related transcription factor A). MAL is itself regulated in vivo by changes in cellular actin dynamics, which alter its interaction with G-actin. The G-actin-sensing mechanism of MAL/MRTF-A resides in its N-terminal domain, which consists of three tandem RPEL repeats. We describe the first molecular insights into RPEL function obtained from structures of two independent RPEL(MAL) peptide:G-actin complexes. Both RPEL peptides bind to the G-actin hydrophobic cleft and to subdomain 3. These RPEL(MAL):G-actin structures explain the sequence conservation defining the RPEL motif, including the invariant arginine. Characterisation of the RPEL(MAL):G-actin interaction by fluorescence anisotropy and cell reporter-based assays validates the significance of actin-binding residues for proper MAL localisation and regulation in vivo. We identify important differences in G-actin engagement between the two RPEL(MAL) structures. Comparison with other actin-binding proteins reveals an unexpected similarity to the vitamin-D-binding protein, extending the G-actin-binding protein repertoire. |
