Structural Biology

A Fuzzy Fit

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Science  27 Jan 2012:
Vol. 335, Issue 6067, pp. 381
DOI: 10.1126/science.335.6067.381-b

Careful tuning of gene regulation is crucial for proper cell function. Temporal or spatial changes in gene expression or changes in gene expression level can compromise cell activity or even viability. Transcriptional activators interact with coactivators, which in turn communicate with the general transcription machinery or chromatin remodeling factors to effect changes in gene expression. Using NMR, Brzovic et al. have examined the structural basis for the binding of the transcriptional activator Gcn4 to the coactivator Mediator subunit Gall11/Med15 (Gal11) in yeast. Activation domains, which are generally rich in acidic residues, often bind diverse coactivators through multiple low-affinity interactions. In this study, the activation domain shows a disordered structure that morphs to a more stable alpha-helical structure upon binding to Gal11. The protein-protein interface is rather simple and consists of only hydrophobic interactions, which allows the activator and coactivator to bind in multiple orientations, forming a so-called “fuzzy” complex. Gcn4 can also interact with other unrelated coactivators using the same residues through a similar mechanism, suggesting that this mechanism may enable transcriptional activators to interact with multiple targets.

Mol. Cell 44, 942 (2011).

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