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Sci. Signal., 14 June 2011
Vol. 4, Issue 177, p. ra40
Polymerization of monomeric actin (G-actin) into filamentous actin (F-actin) underlies changes in cell morphology and motility. The MRTF (myocardin-related transcription factor) group of transcriptional coactivators are actin-binding proteins. They are cytoplasmic in resting cells but accumulate in the nucleus when signal-induced F-actin assembly decreases G-actin concentration. Signals that lead to the formation of F-actin reduce the availability of G-actin and thus promote nuclear localization and activity of MRTF proteins. Mouilleron et al. determined the crystal structure of the actin-binding domain of MRTF-A, which consists of three actin-binding RPEL motifs with two intervening spacer sequences, in association with actin. All five actin binding sites are required to maintain the cytoplasmic localization of MRTF-A in unstimulated cells. These crystal structures reveal how increasing the concentration of monomeric actin—which leads to more molecules of actin binding to each molecule of MRTF-A—traps MRTF-A in the cytoplasm, preventing it from activating target genes. Thus, signal-dependent changes in actins polymerization status can be directly coupled to changes in gene expression.
Citation: S. Mouilleron, C. A. Langer, S. Guettler, N. Q. McDonald, R. Treisman, Structure of a Pentavalent G-ActinMRTF-A Complex Reveals How G-Actin Controls Nucleocytoplasmic Shuttling of a Transcriptional Coactivator. Sci. Signal.4, ra40 (2011).