Mouilleron, S. and Guettler, S. and Langer, C.A. and Treisman, R. and McDonald, Neil Q. (2008) Molecular basis for G-actin binding to RPEL motifs from the serum response factor coactivator MAL. The EMBO Journal 27 (23), pp. 3198-3208. ISSN 1460-2075.
Full text not available from this repository.Abstract
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 RPELMAL peptide:G-actin complexes. Both RPEL peptides bind to the G-actin hydrophobic cleft and to subdomain 3. These RPELMAL:G-actin structures explain the sequence conservation defining the RPEL motif, including the invariant arginine. Characterisation of the RPELMAL: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 RPELMAL structures. Comparison with other actin-binding proteins reveals an unexpected similarity to the vitamin-D-binding protein, extending the G-actin-binding protein repertoire.
| Item Type: | Article |
|---|---|
| School or Research Centre: | Birkbeck Schools and Research Centres > School of Science > Biological Sciences |
| Depositing User: | Administrator |
| Date Deposited: | 04 Aug 2010 14:09 |
| Last Modified: | 17 Apr 2013 12:17 |
| URI: | http://eprints.bbk.ac.uk/id/eprint/1029 |
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