Chemical biology

Designing specificity

Designing molecules that specifically interact with only the intended biological target is a major challenge, especially in therapeutic applications. Grigoryan et al. describe a computational approach to design protein interaction specificity by maximizing the tradeoff between affinity and specificity. They used their approach to design highly selective peptide partners for 19 of 20 families of closely related human basic-region leucine zipper transcription factors.

Grigoryan, G. et al. Nature 458, 859–864 (2009).

Sensors

Fluorescent metabolite sensors

Brun et al. describe a general, modular approach for constructing fluorescence resonance energy transfer (FRET)-based metabolite-sensor proteins. The sensor consists of a Snap tag, a fluorescent protein, a metabolite-binding protein and a synthetic connector that contains both a fluorophore and a ligand that binds to the metabolite-binding protein. In the presence of a target metabolite, which displaces the connector ligand, the 'closed' sensor springs open and results in a change in the FRET efficiency.

Brun, M. A. et al. J. Am. Chem. Soc. 131, 5873–5884 (2009).

Genomics

Identifying protein folding genes

Jonikas et al. describe a strategy to identify Saccharomyces cerevisiae genes involved in protein folding. They harnessed the transcription factor Hac1p, which activates the unfolded protein response, to drive expression of a GFP reporter. They introduced the reporter into ∼4,500 deletion mutant strains and used flow cytometry to monitor single-cell fluorescence, thus identifying genes that either up- or downregulated the expression of the unfolded protein response reporter.

Jonikas, M.C. et al. Science 323, 1693–1697 (2009).

Protein biochemistry

A function for GFP

GFP, a protein found in the humble jellyfish, Aequorea victoria, and its fluorescent protein cousins have had a major impact on biological imaging. However, the biological functions of fluorescent proteins are not well-understood. Bogdanov et al. now report that GFPs can act as light-induced electron donors for various electron acceptors and suggest that they may play a role in cellular processes such as light sensing.

Bogdanov, A. M. et al. Nat. Chem. Biol. advance online publication (26 April 2009).

Nanotechnology

Monitoring enzyme activity in real time

Orosco et al. describe a two-layer porous silicon nanoreactor as a label-free tool to monitor protease activity. The upper layer contains large pores, which trap the protease. The smaller reaction products filter down into the lower layer, which contains smaller pores. This causes a change in optical reflectivity of the silicon nanoreactor, allowing enzyme kinetics to be quantitatively observed in real time.

Orosco, M. M. et al. Nat. Nanotechnol. 4, 255–258 (2009).