A natural-product switch for a dynamic protein interface

Small ligands are a powerful way to control the function of protein complexes via dynamic binding interfaces. The classic example is found in gene transcription where small ligands regulate nuclear receptor binding to coactivator proteins via the dynamic activation function 2 (AF2) interface. Current ligands target the ligand-binding pocket side of the AF2. Few ligands are known, which selectively target the coactivator side of the AF2, or which can be selectively switched from one side of the interface to the other. We use NMR spectroscopy and modeling to identify a natural product, which targets the retinoid X receptor (RXR) at both sides of the AF2. We then use chemical synthesis, cellular screening and X-ray co-crystallography to split this dual activity, leading to a potent and molecularly efficient RXR agonist, and a first-of-kind inhibitor selective for the RXR/coactivator interaction. Our findings justify future exploration of natural products at dynamic protein interfaces

Janet Cardiff : A Survey of Works...

Supplemented by an interview with the artist, Christov-Bakargiev’s essay touches on many aspects of Cardiff’s œuvre and argues that the intimacy of her work leads to a blurring of self and other. Most of the works in the exhibition are represented with images, scripts, artist’s comments and short texts or excerpts of critical commentary from the selected bibliography. The catalogue closes with a comprehensive chronology of Cardiff’s career and an anthology of critical writing. List of works. Bibl. 5 p. 170 bibl. ref

Modulation of t cell signaling by the actin cytoskeleton

10.1242/jcs.098210Journal of Cell Science12651049-1058JNCS