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- Title
Structure of a Pentavalent G-Actin1MRTF-A Complex Reveals How G-Actin Controls Nucleocytoplasmic Shuttling of a Transcriptional Coactivator.
- Authors
Mouilleron, Stéphane; Langer, Carola A.; Guettler, Sebastian; McDonald, Neil Q.; Treisman, Richard
- Abstract
Subcellular localization of the actin-binding transcriptional coactivator MRTF-A is controlled by its interaction with monomeric actin (G-actin). Signal-induced decreases in G-actin concentration reduce MRTF-A nuclear export, leading to its nuclear accumulation, whereas artificial increases in G-actin concentration in resting cells block MRTF-A nuclear import, retaining it in the cytoplasm. This regulation is dependent on three actin-binding RPEL motifs in the regulatory domain of MRTF-A. We describe the structures of pentavalent and trivalent G-actin1RPEL domain complexes. In the pentavalent complex, each RPEL motif and the two intervening spacer sequences bound an actin monomer, forming a compact assembly. In contrast, the trivalent complex lacked the C-terminal spacer- and RPEL-actins, both of which bound only weakly in the pentavalent complex. Cytoplasmic localization of MRTF-A in unstimulated fibroblasts also required binding of G-actin to the spacer sequences. The bipartite MRTF-A nuclear localization sequence was buried in the pentameric assembly, explaining how increases in G-actin concentration prevent nuclear import of MRTF-A. Analyses of the pentavalent and trivalent complexes show how actin loads onto the RPEL domain and reveal a molecular mechanism by which actin can control the activity of one of its binding partners.
- Publication
Science Signaling, 2011, Vol 4, Issue 177, p1
- ISSN
1945-0877
- Publication type
Article
- DOI
10.1126/scisignal.2001750