In the world of biopolymer libraries, Philip Lichtor, core institute member and Merkin Institute for Transformative Technologies in Healthcare director David Liu, and colleagues reported that collections with access to nonpolar side chains outperform libraries without these additions. The researchers created sequence-defined polymer libraries with a variety of charged, polar, and nonpolar side chains, and selected for the ability to bind proteins PCSK9 and IL-6. The libraries with access to nonpolar side chains generally outcompeted other libraries, with more rapid sequence convergence and higher binding affinities. The work also suggests how proteins, which have nonpolar side chains, might have an evolutionary advantage for some tasks compared to nucleic acid polymers that lack these groups. Learn more in Nature Chemical Biology.
Channeling insights about a calcium channel
Mitochondrial calcium uniporter, a transmembrane protein that allows the transport of calcium ions into a cell’s mitochondria, is regulated by two proteins called MICU1 and MICU2. Although it is known that MICU1 and MICU2 work together to inhibit the calcium transport channel, researchers did not completely understand how each of these proteins contributes to this channel's regulation. Reporting in PNAS, Kimberli Kamer, institute member and Metabolism Program co-director Vamsi Mootha, associated scientist Zenon Grabarek at Harvard Medical School, and colleagues provide structural insights about the two proteins, thus explaining the gating mechanism of the uniporter. These findings will further guide disease research, especially in the area of neuromuscular disorder caused by MICU1 deficiency.