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Substrate Sorting by a Supercharged Nanoreactor

Author:
Azuma, Yusuke, Bader, Daniel L. V., Hilvert, Donald
Source:
Journal of the American Chemical Society 2018 v.140 no.3 pp. 860-863
ISSN:
1520-5126
Subject:
catalysts, encapsulation, polypeptides, protein degradation, proteinases, proteins, substrate specificity, zwitterions
Abstract:
Compartmentalization of proteases enables spatially and temporally controlled protein degradation in cells. Here we show that an engineered lumazine synthase protein cage, which possesses a negatively supercharged lumen, can exploit electrostatic effects to sort substrates for an encapsulated protease. This proteasome-like nanoreactor preferentially cleaves positively charged polypeptides over both anionic and zwitterionic substrates, inverting the inherent substrate specificity of the guest enzyme approximately 480 fold. Our results suggest that supercharged nanochambers could provide a simple and potentially general means of conferring substrate specificity to diverse encapsulated catalysts.